pharmacokinetics of ceftriaxone in normal and …
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PHARMACOKINETICS OF CEFTRIAXONE IN NORMAL AND
SALMONELLA TYPHIMURIM INFECTED GOATS
Mossad Gamal El-Din EL Sayed-Ashraf Abd El ndashHakim ElndashKomy Faten Ibrahim EL
Sayed
Faculty of Veterinary Medicine Benha University Egypt Department of Pharmacology
ABSTRACT
The pharmacokinetic parameters of ceftriaxone in blood urine and
milk following intravenous and intramuscular (single amp repeated)
administrations were estimated in normal and experimentally
Salmonella typhimurum infected goats Following a single intravenous
injection of 20 mg ceftriaxonekg bwt in normal goats ceftriaxone
could be detected therapeutically for 8 hours post intravenous
injection The serum concentration ndash time curve of ceftriaxone
following intravenous injection showed that the drug obeyed a two
compartments open model The intramuscular bioavailability of
ceftriaxone in normal goats was 6128 Intramuscular injection of 20
mg ceftriaxone per kilogram body weight twice daily for five
consecutive days in normal and Salmonella typhimurium infected
goats revealed a lower significant serum ceftriaxone concentration after the first third fifth
seventh ninth doses in Salmonella typhimurium infected goats compared with normal goats
The high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular
administrations suggested that ceftriaxone could be used for treatment of mastitis caused by
Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats
The high concentrations of ceftriaxone in urine after repeated intramuscular administrations
suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections
caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in
goats
KEYWORDS Pharmacokinetics ceftriaxone goats
WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES
SJIF Impact Factor 5210
Volume 5 Issue 02 1433-1458 Research Article ISSN 2278 ndash 4357
Correspondence for
Author
Dr Faten Ibrahim EL
Sayed
Faculty of veterinary
medicine Benha
University Egypt
Department of
Pharmacology
Article Received on
19 Dec 2015
Revised on 09 Jan 2016
Accepted on 29 Jan 2016
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INTRODUCTION
Ceftriaxone is a third-generation semi-synthetic bactericidal cephalosporin antibiotic
resistant to various types of bacterial β-lactamases It has excellent activity against gram
negative bacteria as well as a wide range of gram-positive and some anaerobic bacteria
including enterobacteriaceae Streptococcus pneumoniae Haemophilus inflfl uenzae
Pseudomonas aeruginosa and other non-enterococcal streptococci[123]
Like other
cephalosporin ceftriaxone bind to the penicillin-binding proteins (PBP) by covalent bond and
inactivate transpeptidase enzymes thereby inhibiting the peptidoglycan synthesis leading to
inhibition of the cell wall synthesis[4]
It has rapid absorption and wide distribution in tissues
as well as body fluids after parenteral administration in animals[5]
The drug thus seems to be
useful in the treatment of a variety of bacterial infections including meningitis septicemia
pyoderma colibacillosis surgical prophylaxis and urinary tract respiratory tract wound soft
tissue and joint infections[2]
Clinical pharmacology of ceftriaxone was investigated in human[6]
sheep[78]
goats[91011]
buffulo calves[1213]
calves[14]
domestic cats[15]
cross bred cow calves[16]
Little literature was
found concerning the pharmacokinetics of ceftriaxone in goats Thus the aim of present
work was undertaken to study the pharmacokinetic parameters of ceftriaxone after
intravenous and intramuscular injection in normal and experimentally Salmonella
typhimurium infected goats also the bioavailability of ceftriaxone was calculated after a
single intramuscular injection in normal goats
MATERIAL AND METHODS
Drug
Ceftriaxone is a member of third generation cephalosporins ceftriaxone sodium was used in
this study under the trade name (Cefaxonereg) It is available as glass vial containing 1000 mg
ceftriaxone it was produced by Pharco company Egypt
Experimental animals
Four clinically normal lactating baladi four experimentally infected goats and lactating goats
were used for each drug in this investigation The body weight and age of the tested goats
ranged from 20-26 kg and from 2 to 3 years old (for normal goats) and from 22 ndash 29 kg and
from 25 to 35 years old for experimentally infected goats They were housed in hygienic
stable fed on barseem drawa and concentrate Water was provided ad-libitum
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Grouping of goats
Group (1)
It included 4 normal post-partum lactating goats Each goat was injected intravenously into
the left jugular vein ceftriaxone These goats were left for 15 days after the intravenous
injection to insure complete excretion of ceftriaxone from bodies of goats Then each goat
was injected intramuscularly into the gluteus medius muscle with the same dose of
ceftriaxone The aim of intramuscular injection to calculate the bioavailability of ceftriaxone
in normal goats
Group (2)
It included 4 normal post-partum lactating goats Each goat was injected intramuscularly into
the gluteus medius muscle with 20 mgkg bwt ceftriaxone for five consecutive days
Group (3)
It included 4 experimentally infected post-partum lactating goats with twenty four hours
peptone water culture of enterpathogen Salmonella typhimurium which were cultured on
nutrient agar plates for 24 hours then suspension of culture were collected by sterile saline
By opacity tube the required concentration of 2Χ109 micro-organismsml was obtained Each
of the four goats received orally a 10 ml suspension containing 2x109
organismml The
clinical symptoms of bacteraemia as fever and diarrhea appeared after 48-72 hours of
injection with Salmonella typhimurium suspension[17]
Each goat was injected
intramuscularly into the gluteus medius muscle with ceftriaxone per kilogram body weight
48 hours after experimental infection with samlonella Typhmurium for five consecutive days
Collection of samples
Blood samples
Blood samples were collected from right jugular vein following a single intravenous injection
of ceftriaxone in normal goats blood samples were collected after 5 min 10 min15 min 30
min 1 2 4 8 and 12 hours of administration Blood samples following the second third
fourth and fifth intramuscular doses were collected before and 10 min 15 min 050 1 2 4 8
and 12 hours post injection Blood samples taken from goats were allowed to clot and the
serum separated by centrifugation collected and divided in to two parts the first part was
used for assay of ceftriaxone and the second part was used for creatinine assay All serum
samples were stored at ndash 20degC until assay for ceftriaxone and creatinine
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Urine samples
The urine sample was taken by using rubber balloon catheter (Folatex No 4158512) The
goats were catheterized and bladder was evacuated before each experiment Following
injection of ceftriaxone (single intravenous single intramuscular and repeated intramuscular
administration) in goats (normal and experimentally infected) urine samples were taken after
025 050 1 2 4 8 12 24 and 48 hours of administrations Urine sample which was taken
at 025 h was discarded Urine samples from goats of group (1) group (2) group (3) were
collected and divided into two parts the first part was used for assay of ceftriaxone and the
second part was used for creatinine assay All urine samples were stored at - 20degC until assay
for ceftriaxone After the end of each experiment the urinary bladder was irrigated with 15
milliliters potassium permanganate solution 1 5000 as antiseptic agent
Milk samples
The udder was completely evacuated before drug administration and milk samples were
collected by hand stripping from both teats Following injection of ceftriaxone (single
intravenous single intramuscular and repeated intramuscular administration) in goats (normal
and experimentally infected) milk samples were taken after 050 1 2 4 8 12 24 and 48
hours of administrations Milk sample which was taken at 025 h was discarded The udder of
each goat in all groups was completely evacuated before drug administration and after each
milk samples Milk samples from goats of all groups were allowed to clot (by mixing equal
volumes of milk and 25 trichloroacetic acid) and centrifuged The skim milk was collected
and stored at ndash 20degC until assay for ceftriaxone
Analytical Procedure
Assay of ceftriaxone
Ceftriaxone was assayed in goats serum distalled water and goats milk by microbiological
method using agar well diffusion method by using of Escherichia coli ATCC (American
type culture collection 25922) as tested microorganism which was obtained from
Microbiological Department Animal Health Institute Doky Giza Egypt)[18]
Concentrations of ceftriaxone in biological fluids were determined by modification of the
agar ndash plate diffusion method[19]
using Escherichia coli ATCC25922 as assay organism and
Muller Hinton agar media
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Assay of samples
According to[20]
three plates were used for each sample Six pores were made three of them
were filled with reference concentration while the other three pores were filled with the
serum milk or urine samples in triplicate manner The plates were incubated at 37degC for 18
hours then the diameter of inhibitory zones were measured The diameter of inhibitory zones
of samples were corrected by using the zone diameter of the reference concentration in the
same manner as previously discussed either by addition or subtraction From the standard
curve the concentrations corresponding to the corrected values of the inhibitory zones were
obtained
Drug clearance
Clearance of the tested drug from the blood of goats was estimated according to the following
equation
Drug clearance10 kg b wt =
Drug concentration in urine (microgml) X rate of diuresis (mlmin) Body weight (Kg)
_________________________________________________________________
Drug concentration in serum (microgml) X 10
Assay of creatinine in serum and urine
Creatinine was assayed by[21]
and performed by kit manufactured by Diamond diagnostics
company
Creatinine clearance
The creatinine clearance (mlmin10 kgbwt) for goats was calculated by the following
equation
Creatinine clearance 10 kgbwt =
Creatinine concentration in urine (mgL) X rate of diuresis (mlmin) Body weight (Kg)
______________________________________________________________________
Creatinine concentration in serum (mgL) X 10
Pharmacokinetic analysis
The pharmacokinetic parameters were calculated by using Winonlin version 12 and other
parameters according to[2223]
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Statistical Analysis
The data were calculated as mean plusmn standard error All statistical analysis were carried out
according to[24]
using the scientific calculator CASIO fx 120
RESULTS
Following a single intravenous injection of 20 mg ceftriaxonekg bwt in normal goats
ceftriaxone could be detected therapeutically for 8 hours post intravenous injection The
serum concentration ndash time curve of ceftriaxone following intravenous injection showed that
the drug obeyed a two compartments open model (Figure 1) The disposition kinetics of
ceftriaxone following a single intravenous intramuscular injection were recorded in table (1)
Intramuscular injection of 20 mg ceftriaxone per kilogram body weight twice daily for five
consecutive days in normal and Salmonella typhimurium infected goats revealed a lower
significant serum ceftriaxone concentration after the first third fifth seventh ninth doses in
Salmonella typhimurium infected goats compared with normal goats The pharmacokinetic
parameters of ceftriaxone after repeated intramuscular injection in normal were compared to
those in Salmonella typhimurium infected goats (Table 2) and (Figure 2 amp 3)
The highest concentrations of ceftriaxone in milk were recorded 4 hours after each
intramuscular dose (Table 3) with a significant lower value in Salmonella typhimurium
infected goats compared with normal goats The calculated milkserum concentrations ratios
of ceftriaxone after repeated intramuscular injection (Table 4)
The amount of urine (mlmin) voided after repeated intramuscular injection of 20 mgkg bwt
Twice daily of ceftriaxone for five consecutive days in normal and experimentally
Salmonella typhimurium infected goats were recorded in table (5) The mean peak urine
concentrations of ceftriaxone (Table 6) were reached 2 hours after each intramuscular dose
with a lower significant concentration in Salmonella typhimurium infected goats compared
with normal goats Urineserum concentration ratios of ceftriaxone after repeated
intramuscular injection in normal and experimentally Salmonella typhimurium infected goats
were calculated and illustrated in table (7) Creatinine clearance (mlmin10 kg bwt)
expressing glomerular filtration rate from blood of goats was shown in table (8) The rate of
ceftriaxone clearance (mlmin10 kg bwt) from blood of goats was shown in table (9) The
ratio between ceftriaxone clearance and creatinine clearance was calculated and illustrated in
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table (10) The data revealed a significant lower ratio in Salmonella typhimurium infected
goats compared with normal goats after the third fifth seventh ninth doses
Table (1) Pharmacokinetics parameters of ceftriaxone (μgml) following a single
intravenous and intramuscuer injection of 20 mgkg bwt in normal goats (n=4)
Intramusculer_
(XplusmnS E)
Intravenous_
(XplusmnS E) Unit Parameters
-------- 1213 plusmn321321 microgml Cdeg
4360plusmn12343 61390 plusmn330 microgml A
43440plusmn43660 636 plusmn43316 h-1
α
43433plusmn3340 43340 plusmn43442 H (α) 43 T
43420plusmn43233 4333plusmn131 h-1
K12
43446plusmn43400 43409plusmn231 h-1
K21
-------- 43440plusmn431 lkg Vdss
4321plusmn6340 43636plusmn1303 microgml B
434446plusmn43419 43443plusmn43136 h-1
β
43141plusmn39340 43411plusmn331 H t05(β))
4344plusmn43401 434440plusmn43409 lkgh Cl tot
-------- 1136plusmn2111300 microgmlh AUMC
-------- 43303 plusmn0314 H MRT
9300plusmn2439 30plusmn034330 microgmlh AUC
3392plusmn63329 -------- F
43436plusmn4361 -------- h-1
K01
43420plusmn3346 -------- h-1
T05(k01)
4342plusmn330 -------- H Tmax(calc))
43021plusmn04343 -------- μgml Cmax(calc)
Cdeg Drug concentration in the serum at zero time immediately after a single intravenous
injection (μgml) A amp B Zero time plasma drug concentration intercepts of biphasic
intravenous disposition curve The coefficient B is based on the terminal exponential phase
(μgml) α amp β Hybrid rate constant of biphasic intravenous disposition curve values of α
and β are related to the slopes of distribution and elimination phase respectively of
biexponential drug disposition curve (h-1
) T05 (α) Distribution half ndash life (h) t05 (β)
Elimination half ndash life (h) K12 First ndash order transfer rate constant for drug distribution from
Central to peripheral compartment (h-1
) K21 First order transfer rate constant for drug
distribution from Peripheral to central compartment (h-1
) Vdss The apparent volume of
distribution which was calculated by steady ndash state method (mlkg) AUMC Area under
moment curve MRT Mean residence time AUC Total area under the serum drug
concentration versus time curve from t = 0 to t = α after administration of a single dose F
Bioavailability Cmax maximum drug concentration Tmax time of maximum observed
concentration in blood
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Figure (1) Arthimatic plot of Serum concentrations of ceftriaxone (μgml) in normal
goats following a single intramuscular injection )diamsdiams( previously given the same doseby
a single intravenous injection () of 20 mg ceftriaxonekgbwt (n=4)
Figure (2) Semilogarthmic graph depicting the time course of ceftriaxone in serum of
normal goats following repeated ntramuscular injection of 20 mg ceftriaxonekgbwt
twice dialy for five consecutive days (n=4)
Figure (3) Semilogarthmic graph depicting the time course of ceftriaxone in serum of
experimentally Salmonella typhimurim infected goats following repeated ntramuscular
injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4) 3
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Table (2) Pharmacokinetic parameters of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected
goats following repeated ntramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)
Dose
Unit
عىهParameters
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1269plusmn0073 7409plusmn121 1352plusmn0132 6373plusmn147 1410plusmn0243 5923plusmn126 1461plusmn0214 5430plusmn125 1424plusmn0172 7635plusmn176 gmlmicro A
0651plusmn0049 plusmn000843116 0720plusmn0008 plusmn00413300 0823plusmn0006 plusmn00263322 0848plusmn0025 plusmn00233323 0786plusmn0028 133plusmn0033 h-1 Α
106plusmn0008 330plusmn0015 0962plusmn0011 0392plusmn0007 0841plusmn0007 0567plusmn012 0818plusmn0024 0569plusmn0012 0885plusmn0030 plusmn00124322 H T05(α)
248plusmn0019 168plusmn0047 203plusmn0075 181plusmn0033 267plusmn0039 120plusmn0028 248plusmn0060 122plusmn0026 222plusmn0100 136plusmn0027 h-1 Kab
0278plusmn0002 0412plusmn0009 0342plusmn0012 0383plusmn0008 0252plusmn0009 0567plusmn0011 0279plusmn0005 00569plusmn0011 0314plusmn0014 0 510plusmn0012 H T05(ab)
0627plusmn0008 0378plusmn0007 0430plusmn0008 0402plusmn0008 0113plusmn00027 0424plusmn0009 0117plusmn0004 0394plusmn0008 0116plusmn0003 0239plusmn0005 h-1 K12
121plusmn0013 0962plusmn0022 141plusmn0021 130plusmn0023 0666plusmn0019 0651plusmn0013 0683plusmn0020 0660plusmn0013 0761plusmn0039 0998plusmn0023 h-1 K21
115plusmn0035 129plusmn0026 104plusmn0047 112plusmn0024 106plusmn0037 122plusmn0025 110plusmn0077 119plusmn0023 0910plusmn0032 123plusmn0023 H Tmax
4182plusmn0628 6108plusmn140 3440plusmn0363 5135plusmn0860 3117plusmn0965 4774plusmn0854 2713plusmn0781 4243plusmn0 870 2479plusmn0547 4065plusmn0825 gmlmicro Cmax
4944plusmn0820 7195plusmn142 4199plusmn0702 6511plusmn130 3190plusmn0688 5117plusmn113 3185plusmn0909 4709plusmn0990 3256plusmn0918 6329plusmn139 gmlmicro B
0164plusmn0003 0189plusmn00043 0181plusmn0002 0178plusmn0004 0181plusmn00035 0167plusmn0004 0214plusmn0009 0195plusmn0005 0249plusmn0918 0272plusmn0006 h-1 β
423plusmn0079 367plusmn0086 381plusmn0047 388plusmn0089 382plusmn0074 415plusmn0081 325plusmn0139 355plusmn0075 277plusmn0056 255plusmn0050 H T05β
0879plusmn0015 0429plusmn0009 109plusmn0004 0426plusmn0009 133plusmn0022 0503plusmn0011 154plusmn0064 0675plusmn0013 171plusmn0060 0693plusmn0014 Lkgh Cltot
28358plusmn215 40775plusmn808 21784plusmn0888 34259plusmn720 17860plusmn155 30705plusmn601 15281plusmn239 24135plusmn555 12175plusmn144 20292plusmn487 gmlhmicro AUC
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (3) Milk concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats
following repeated ntramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)
Dose Time of
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
197plusmn0205 200plusmn0408 125plusmn0104 155plusmn0132 0887plusmn0013 0885plusmn014 0500plusmn0040 074plusmn0012 ------------ ------ Before
200plusmn0408 22plusmn0108 197plusmn0205 200plusmn0408 155plusmn0132 197plusmn0205 100plusmn000 155plusmn0132 ----------- -------- 050
526plusmn0166 700plusmn0408 300plusmn0408 64plusmn0163 25plusmn0204 600plusmn0408 155plusmn0132 582plusmn0118 100plusmn000 520plusmn0166 1
640plusmn0163 900plusmn0408 582plusmn0118 792plusmn0114 582plusmn0118 755plusmn0221 275plusmn0061 700plusmn0408 200plusmn0408 691plusmn0176 2
900plusmn0408 1512plusmn0125 640plusmn0163 1475plusmn0322 640plusmn0163 1400plusmn0408 600plusmn0408 1352plusmn0205 526plusmn166 1225plusmn0595 4
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350plusmn0353 400plusmn0408 300plusmn0408 392plusmn0125 300plusmn0408 35plusmn0353 275plusmn006 300plusmn0408 155plusmn0132 275plusmn0061 6
300 plusmn0408 35plusmn0353 125plusmn0104 200plusmn0408 125plusmn0104 155plusmn01 0825plusmn0062 100plusmn000 0500plusmn0040 0887plusmn0013 8
200plusmn0408 22plusmn0108 100plusmn000 155plusmn0132 100plusmn000 125plusmn0104 0730plusmn002 0825plusmn0078 0422plusmn000 073plusmn0020 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (4) Milkserum concentrations ratios of ceftriaxone in normal and experimentally Salmonella typhimurim infected
goats following repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice daily for five consecutive days (n=4)
Dose Time of
a
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
0400plusmn0049 025plusmn0063 0307plusmn0026 021plusmn0019 0365plusmn00064 016plusmn0026 0232plusmn0016 0205plusmn0002 -------- helliphelliphelliphellip Before
0057plusmn0125 0042plusmn00025 0062plusmn00062 0042plusmn0010 0575plusmn00062 0055plusmn0006 0067plusmn0016 0049plusmn0005 --------- -------- 050
0127plusmn00062 0115plusmn00064 008plusmn0012 0117plusmn0004 0088plusmn00054 0122plusmn0008 008plusmn0017 0126plusmn0028 0039plusmn0005 0122plusmn0004 1
018plusmn0008 0185plusmn0010 021plusmn0004 017plusmn0004 0182plusmn0054 0179plusmn0006 0112plusmn00025 0193plusmn0012 0097plusmn0020 019plusmn0004 2
0357plusmn0020 0425plusmn0005 033plusmn0021 045plusmn0009 0285plusmn0082 0494plusmn0015 0395plusmn0016 0572plusmn001 0415plusmn0017 054plusmn0027 4
018plusmn0015 016plusmn0016 0207plusmn0022 0175plusmn0006 0257plusmn0037 0180plusmn0017 0272plusmn0015 0201plusmn003 0196plusmn0016 0222plusmn0002 6
0212plusmn0033 0212plusmn0020 0200plusmn0044 0122plusmn0024 0152plusmn0011 014plusmn0022 0122plusmn00062 0102plusmn0001 0107plusmn00094 0117plusmn0002 8
0372plusmn0042 025plusmn001 0325plusmn0027 0192plusmn0014 0265plusmn00064 0185plusmn0015 0272plusmn0125 0195plusmn0012 0252plusmn0032 0275plusmn0009 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
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Table (5) The amount of urine (mlmin) voided in normal and experimentally Salmonella typhimurim infected goats following
repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)
Dose Time of a
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
plusmn00372344 126plusmn0034 130plusmn0030 130plusmn0028 118plusmn0066 118plusmn0067 108plusmn0013 108plusmn0008 ----------- -------- Before
0577plusmn0069 43494057plusmn 045plusmn0060 plusmn0064309 0312plusmn002 033plusmn0012 0340plusmn0024 033plusmn0012 0287plusmn0017 0272plusmn0014 050
0712plusmn0019 0692plusmn0014 068plusmn0081 0697plusmn0006 0672plusmn0011 0675plusmn 0009 0635plusmn0032 0655plusmn0010 0719plusmn0031 0697plusmn0015 1
0837plusmn0025 0787plusmn0021 0732plusmn0011 plusmn00054300 0715plusmn0011 0715plusmn002 0722plusmn0019 0702plusmn0018 0737plusmn0027 0762plusmn0041 2
0535plusmn0095 0507plusmn0021 0447plusmn0022 0452plusmn002 0402plusmn0075 0405plusmn0011 0400plusmn0057 0397plusmn0009 0380plusmn0004 038plusmn001 4
0437plusmn00094 0432plusmn0008 0400plusmn0010 0405plusmn0002 0380plusmn0007 plusmn00044319 0372plusmn0047 037plusmn 0007 0350plusmn0005 0365plusmn0006 6
0397plusmn0028 0410plusmn0008 0380plusmn0012 0395plusmn0009 0355plusmn0086 0352plusmn0007 0340plusmn0004 0345plusmn0005 0302plusmn0004 0335plusmn0005 8
0385plusmn001 0380plusmn0010 0385plusmn00064 0380plusmn0008 0365plusmn0064 0367plusmn0004 0362plusmn0086 0372plusmn0106 0327plusmn0006 0362plusmn0016 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (6) Urine concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats
following repeated intramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)
Dose Time of a
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1125plusmn150 1125plusmn15 735plusmn287 81plusmn324 183plusmn03 555plusmn798 37plusmn0811 1815plusmn43290 -------------- ------ Before
2415plusmn357 2625plusmn374 1695plusmn788 249plusmn574 10575plusmn64 2415plusmn357 5400plusmn273 2085plusmn991 102plusmn160 168plusmn547 050
26025plusmn787 2923plusmn479 22425plusmn1225 2805plusmn35 1695plusmn618 2705plusmn471 10200plusmn547 2415plusmn357 6975plusmn225 22425plusmn894 1
29295plusmn765 3012plusmn346 28575plusmn738 2964plusmn415 2355plusmn259 2923plusmn479 1635plusmn561 2645plusmn917 102plusmn547 24825plusmn616 2
23475plusmn430 2482plusmn616 23475plusmn1564 2415plusmn357 1695plusmn788 198plusmn848 8475plusmn309 1515plusmn708 60plusmn212 1185plusmn45 4
1905plusmn45 2355plusmn259 153plusmn519 1935plusmn960 114plusmn948 159plusmn173 6675plusmn309 1215plusmn45 1312plusmn0552 855plusmn193 6
153plusmn1024 1965plusmn135 1335plusmn1229 150plusmn34 735plusmn295 1365plusmn665 6181plusmn339 72plusmn244 907plusmn0951 5025plusmn143 8
135plusmn519 120plusmn346 11725plusmn1551 96plusmn874 525plusmn295 75plusmn173 153plusmn130 39plusmn212 3735plusmn0458 13125plusmn0552 12
Between normal and diseased
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Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (7) Urineserum concentrations ratios of ceftriaxone following repeated ntramuscular injection of 20 mg
ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats
(n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
229plusmn 163 1448plusmn0743 1885plusmn159 1125plusmn0484 533plusmn0260 1050plusmn358 175plusmn0380 4146plusmn116 ------- ------ Before
741plusmn0063 plusmn01553 58plusmn0242 plusmn0149390 422plusmn0206 683plusmn0106 245plusmn0092 667plusmn0306 0510plusmn0081 559plusmn0181 050
651plusmn0243 plusmn0065031 637plusmn0373 plusmn014431 565plusmn0243 plusmn0085300 360plusmn0303 plusmn0110312 279plusmn0121 534plusmn0248 1
836plusmn0150 plusmn00476322 862plusmn0180 plusmn010463 942plusmn0166 plusmn0130631 217plusmn0303 727plusmn0256 508plusmn0186 plusmn01680340 2
939plusmn0235 plusmn01580344 1006plusmn0710 plusmn00750310 999plusmn0542 plusmn02850344 565plusmn0223 641plusmn0241 48plusmn0164 plusmn014834 4
1005plusmn0418 2plusmn018813 1097plusmn0641 plusmn03979300 993plusmn0921 plusmn0252931 619plusmn0483 plusmn0362933 167plusmn0101 642plusmn0644 6
1091plusmn0649 plusmn075332339 1171plusmn0980 995plusmn0415 925plusmn0593 plusmn05593433 886plusmn0408 plusmn02510311 2055plusmn0311 plusmn02046310 8
2392plusmn129 plusmn032731396 1794plusmn0228 1222plusmn124 1418plusmn109 plusmn026733336 580plusmn0397 plusmn03951326 227plusmn0452 plusmn02740316 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (8) Creatinine clearance (mlmin10kgbwt) following repeated intramuscular injection of 20 mg ceftriaxonekgbwt
twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats (n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1115plusmn0703 2265plusmn167 481plusmn0409 672plusmn0817 669plusmn0672 1202plusmn0777 695plusmn0634 1724plusmn179 ----------- ------ Before
0703plusmn0091 147plusmn0305 0718plusmn0141 251plusmn0707 0547plusmn0055 0699plusmn0092 0802plusmn0099 103plusmn0106 295plusmn0124 0458plusmn0037 050
101plusmn0075 161plusmn0093 131plusmn0099 264plusmn0217 161plusmn0146 373plusmn0499 247plusmn0110 4755plusmn0582 214plusmn0234 103plusmn0166 1
157plusmn0198 387plusmn0340 173plusmn0501 267plusmn0217 187plusmn0563 287plusmn0499 451plusmn0223 972plusmn105 263plusmn0399 169plusmn0454 2
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
184plusmn0095 346plusmn0444 173plusmn0501 436plusmn0599 383plusmn0299 682plusmn0584 328plusmn0253 119plusmn153 123plusmn0057 292plusmn0742 4
221plusmn0242 411plusmn0661 241plusmn0186 663plusmn0584 308plusmn0234 422plusmn0314 353plusmn0393 548plusmn0901 105plusmn0057 264plusmn0294 6
261plusmn0295 476plusmn0339 319plusmn0273 753plusmn0676 106plusmn0207 0773plusmn0049 228plusmn0175 456plusmn0340 206plusmn0160 404plusmn0419 8
310plusmn0218 409plusmn0434 3264plusmn0153 669plusmn0476 209plusmn0189 235plusmn0337 217plusmn0143 377plusmn0342 240plusmn0218 6055plusmn0176 12
Between normal and diseased
Plt 005 Plt001 Plt0001
Table (9) Ceftriaxone clearance (mlmin10kgbwt following repeated intramuscular injection of 20 mg ceftriaxone kgbwt
twice in normal and experimentally Salmonella typhimurim infected goats (n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1048plusmn121 0557plusmn684 895plusmn113 0547plusmn560 238plusmn0222 103plusmn 480 0668plusmn0157 0173plusmn216 -------- ----------- Before
156plusmn0251 43204plusmn3322 0936plusmn0162 43211plusmn3334 0473plusmn0037 43469plusmn43964 0300plusmn0028 43341plusmn080 0190plusmn0137 43400plusmn43642 050
166plusmn0079 43323plusmn3311 157plusmn0178 43419plusmn3301 137plusmn0115 43311plusmn33022 0883plusmn0054 43341plusmn 133 0616plusmn0153 43120plusmn3301 1
254plusmn0272 43361plusmn3391 222plusmn0093 4331plusmn3390 243plusmn0180 43209plusmn3309 183plusmn0149 43310plusmn2340 128plusmn0153 43312plusmn3390 2
181plusmn0136 43339plusmn3316 161plusmn0129 433plusmn3329 144plusmn0100 43412plusmn3349 0821plusmn0072 0063plusmn0977 0654plusmn0065 43400plusmn4306 4
160plusmn0177 43393plusmn336 152plusmn0200 43416plusmn331 135plusmn0118 4332plusmn3322 0897plusmn0052 43304plusmn3330 0212plusmn0022 43460plusmn43112 6
153plusmn0049 43291plusmn234 163plusmn0242 43346plusmn3300 0891plusmn0272 43306plusmn3310 108plusmn0071 43416plusmn04310 0229plusmn0046 43490plusmn43916 8
340plusmn0522 43214plusmn2341 249plusmn0150 43112plusmn3393 186plusmn0159 43320plusmn336 0773plusmn0094 43390plusmn 134 0264plusmn0043 43400plusmn 54369 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
Table (10) Ceftriaxone clearancecreatinine clearance following repeated ntramuscular injection of 20 mg
ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats
(n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
0934plusmn0083 0305plusmn0013 183plusmn0116 0864plusmn0098 0358plusmn0018 0279plusmn0047 0099plusmn0020 0127plusmn0001 ------- ----------- Before
220plusmn0115 0819plusmn0044 131plusmn00414 0458plusmn0029 0876plusmn0063 126plusmn0068 0361plusmn0011 0813plusmn0031 0018plusmn0003 108plusmn0062 050
164plusmn0078 0818plusmn0029 118plusmn0068 0546plusmn0027 0858plusmn0052 0407plusmn0041 0331plusmn0009 0287plusmn0025 0324plusmn0011 0909plusmn0187 1
161plusmn0044 0488plusmn0005 232plusmn128 0329plusmn0027 169plusmn0464 0686plusmn0050 0409plusmn0020 0220plusmn0029 0512plusmn0077 266plusmn177 2
0933plusmn0024 0394plusmn0005 0948plusmn0062 0296plusmn0007 0381plusmn0027 0160plusmn0008 0235plusmn0014 0083plusmn0006 0528plusmn0028 0362plusmn0041 4
0726plusmn0018 0411plusmn0028 0639plusmn0066 0204plusmn0006 0446plusmn0034 0286plusmn0008 0238plusmn0019 0214plusmn0006 020plusmn0013 0382plusmn0028 6
0609plusmn0072 0425plusmn0036 0508plusmn0052 0192plusmn0009 0524plusmn0146 174plusmn0083 0477plusmn0015 0213plusmn00018 0109plusmn0185 0222plusmn0006 8
108plusmn0128 0496plusmn0012 0942plusmn0004 0265plusmn0030 0891plusmn0056 0706plusmn0103 0351plusmn0022 0354plusmn0018 0111plusmn0021 0098plusmn0018 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
DISCUSSION
In the present investigation intravenous injection of 20 mg ceftriaxonekgbwt in normal goats the drug showed high serum level
(92plusmn 0408 μgml) at 5 minutes post-injection then its concentration was decreased gradually till reached its minimum level (18
plusmn0816μgml) at 8hours post-injection
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In the present investigation the intravenous injection of 20 mg ceftriaxonekgbwt In normal
goats showed that the drug disposition best fitted a two-compartments- open model a
compartment of plasma and rapid equilibrating tissues and a deeper slower compartment
The obtained result is consistent with those reported for ceftriaxone in lactating goats[9]
lactating ewe[25]
domestic cat[15]
calves[26]
and patanwadi sheep[8]
Also this phenomenon is
in agreement with those reported for other cephalosporines as ceftazidime in a rabbit[27]
cefepime in dog and neonatal foals[28]
ewes[29]
ceftriaxone in goats[9]
cefipime in calves[30]
ceftiofur in cross-bred friesian cattle[31]
cefipime in calves[32]
ceftiofur in cows[33]
cefpirome
in cross-bred calves[3]
cefazidime in goats[35]
and cefquinome in sheep and goats[36]
cefipime
in chickens[37]
Ceftriaxone was distributed after intravenous injection with a distribution phase (α) equal to
656 per hour with a short distribution half ndash life [t05 (α)] equal to 0104 hour The shorter
distribution half-life of ceftriaxone in goats suggested the rapid distribution of the drug in
body tissue and fluid and that nearly similar to that recorded for ceftriaxone in lactating
goats(012 hour)[9]
for ceftriaxone in lactating ewes (0152 hour)[2]
and for ceftriaxone in
calves( 013hour)[26]
The rapid distribution of ceftriaxone in goats is supported by high rate constant of transfer of
the drug from central to peripheral compartment [K12 = 353 h-1
] as compared to the rate
constant of transfer of the drug from peripheral to central compartment [K21= 295 h-1
] This
value is nearly similar to those reported for cefotaxime in goats (K21=327 h-1
)[38]
On contrast
this value was higher than those recorded for ceftriaxone in lactating goats (K21=143 h-1
)[9]
in
lactating ewes (K21=125 h-1
)[25]
and in domestic cats (K21=154 h-1
)[15]
The apparent volume of distribution of ceftriaxone was (0355plusmn0004LKg) this value is
nearly similar to that recorded for cefaronide in sheep(039 LKg)[7]
cefotaxime in dog (048
lkg)[39]
in goat (051 lkg)
[40] for caphalexin in buffalo calves (041 Lkg)
[41] for cefipime in
ewes and calves (032 lkg) (043Lkg)[29]
and[30]
respectively For ceftriaxone in domestic
cats (057Lkg)[15]
in camel (032Lkg)[42]
On the other hand this result is differ than that
reported for cefotaxime in buffalo calves (117Lkg)[43]
High value of the volume of
distribution suggested extensive penetration power Drug with volume of distribution greater
than one literkilogram indicated wide distribution or extensive tissue binding or both[44]
The
apparent volume of distribution in the present study indicated moderate tissue penetrating
power This result agreed with[15]
for ceftriaxone in domestic cats
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Ceftriaxone is eliminated in the current study following a single intravenous injection with
elimination half ndashlife [t 05(β)] equal to 519 hours This observation is nearly agreed with the
data recorded for ceftizoxime in goats (624hours)[45]
On contrast this value was longer than
that reported for ceftriaxone in lactating ewe (175hours)[25]
for cefaronide in sheep (17
hours)[7]
For cephalexin in buffulo calves (216hours)[41]
for ceftriaxone in healthy horse
(162hours)[46]
also this value is longer than that recorded for ceftriaxone in lactating goats
(144hours)[9]
for cefipime in goats (186hours)[47]
The rate of total body clearance of ceftriaxone following a single intravenous injection is
0048 lkgh which equal to data reported for ceftizoxime in lactating goats (005Lkgh)[45]
On contrast this value is lower than that reported for ceftriaxone in buffulo calves lactating
goats buffulo calves (Bubalus bubalis) goats (capra hircus) patanwadi sheep (026 Lkgh)
(395 Lkgh) (440 Lkgh) (450 Lkgh) (391 Lkgh)[12913118]
respectively
The variation in total body clearance might be attributed to specific interspecies variation
handling of the drug method used healthy status of the animal[48]
The difference between values calculated for pharmacokinetic parameters may be attributed
to animal species the drug formulation employed the age the size or sex o l lf the animal
or even inter individual variation and also due to method of analysis of the drug[49]
Following a single intramuscular injection of 20 mg ceftriaxonekg bwt In normal goats the
drug reached its peak serum concentrations after one hour of injection with value
of(41μgml) Ceftriaxone could be detected in serum in a therapeutic level (263μgml) at 12
hours post-injection The reported peak serum concentrations neerly similar to that reported
for cephalexin in buffulo calves (457 microgml)[41]
These results is differed than those reported
for ceftriaxone in cross breed calves (188 microgml at 30 min[16]
in Kangro breed of goats
(Capra Hircus) (2640 microgml at 20 min[10][50]
found after intramuscular administration of
ceforazone peak plasma concentration was (976 microgml) at 45min This result was also higher
than that recorded for ceftriaxone in buffalo calves (158 microgml)[13]
The calculated maximum serum concentration (Cmax) is (40015 microgml) at maximum time
(tmax) of 157 hours The reported (Cmax) agreed with the data reported for cefipime in goats
(4932 microgml[47]
The reported maximum serum concentration (Cmax) is higher than that
reported for ceftriaxone in lactating goats(236 microgml)[9]
in lactating ewes (1722 microgml[25]
in
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
goats (2151 microgml)[11]
for cefquinome in camels (123 microgml)[51]
for ceftriaxone in calves
(1534 microgml)[26]
in patanwadi sheep (1553 microgml)[8]
for cefpirome in cattle (101 microgml)[52]
And for ceftiofur in chickens (2594 μgml)[37]
On the other hand the result was lower than
that reported by[6]
who observed the maximum serum concentration (Cmax) of ceftriaxone in
human after ntramuscular administration was (805 microgml) also it was lower than that
reported for ceftriaxone in dog (11510 microgml)[53]
in domestic cats (5440 microgml)[15]
and for
ceftazoxime in goats (8878 microgml)[45]
The reported [tmax] is neerly similar to that reported for ceftriaxone (104hours)in lactating
ewes by[25]
On contrast it is longer than those reported for ceftriaxone in dogs
(129hours)[53]
for ceftriaxone in lactating goats (07hours)[9]
also the result was longer than
that reported for ceftriaxone in domestic cats (033hours)[15]
in buffulo calves (05 hours)[13]
and for cefpirome in cattle (075hours)[52]
The reported [tmax] is shorter than those reported
for cefquinome in camels (425hours)[51]
in sheep and goats (261 and 262 hours)[36]
and for
ceftiofur in chickens (251 hours)[37]
The elimination half life [t05(β)]
following a single intramuscular administration was 1804 hours This value is nearly agreed
with that recorded for cefquinomein camels (1024hours)[52]
On contrast this result is longer
than that reported for cephalexin in buffalo calves (243hours)[41]
for ceftriaxone in lactating
ewes (177hours)[25]
in buffalo calves (438hours)[13]
in goats (203 hours)[11]
and for
cefipime in goats (165 hours)[47]
The rate of total body clearance of ceftriaxone following a single intramuscular injection is
0043lkgh This value was lower than that reported for ceftriaxone in buffulo calves
(401Lkgh)[13]
in goats (304 Lkgh)[11]
and in sheep (222 Lkgh)[8]
Bioavailability is the fraction of the drug administered by non vascular rout that gains
accesses to the systemic circulation The obtained result revealed that the calculated systemic
bioavailability percent was 6128 It is equal to that recorded for cefpirome in cow calves
(61)[54]
It is nearly equal to that recorded for ceftriaxone in sheep (64)[8]
On the other
hand this value is higher than those recorded for cefperazone in crossbred calves (481)[50]
for ceftriaxone in goats (59)[11]
in calves (47)[55]
On contrast this value is lower than
those reported for cefotaxime in two cats 982 and 93)[57]
for cephradine in goats
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
(739)[58]
for ceftazidime in a rabbit (966)[27]
for ceftriaxone in lactating goats (85)[9]
in lactating ewes (836)[25]
in domestic cats 8572[15]
for cefipime in goats 8645[47]
for ceftriaxone in buffulo calves 702[13]
and for ceftiofur in chickens 8890[37]
Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium
infected goats twics dialy for five days revealed that the drug could be detected in a
therapeutic level for 12hours following repeated intramuscular administrations and exceeded
the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]
The relative higher serum concentrations of ceftriaxone after the last dose compared to the
first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12
hours intervals for five consecutive days These observations agreed with data reported by[36]
on comparing the data of serum levels of repeated intramuscular injections with first
intramuscular injection it was revealed that repeated intramuscular injections of cefquinome
have cumulative effect in both species sheep and goats
The obtained result is inconsistent with that reported by[56]
who found thatwhen cefotaxime
was administered repetitively in patients the ratio of maximal serum levels after the last dose
to those after the first dose demonstrated minimal accumulation of intact drug and by[60]
who
found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in
buffalo calves
The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium
infected goats are significantly lower than those in normal goats following repeated
intramuscular injection These lower blood concentrations in Salmonella typhimurium
infected goats might be attributed to the higher penetrating power of ceftriaxone to the
diseased tissues[48]
This phenomenon is similar to data recorded by[61]
who suggested that
Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of
ceftriaxone These alterations might be due to fever and inflammation induced by
infections[59]
proved that the serum concentrations of cephradine following intramuscular
administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after
each intramuscular dose with a lower significant values recorded in Escherichia-coli infected
goats than in normal goatsAlso similer to that reported by[62]
who observed that the
maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
in comparison to normal sheepOn contrast[43]
reported that peak plasma level of cefotaxime
in febrile buffalo calves was higher than healthy buffalo calves
In this study the total body clearance (CLtot) in normal goats are significantly lower than in
Salmonella typhimurium infected goats This result supported by[61]
and[63]
fever and
inflammation are cardinal features in bacterial infection which may in turn caused an
increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all
these could lead to increased in the rate at which the drug was delivered to both organs which
were important sites of drug excretion This might somewhat explain the increase in the total
body clearance in infected goats This result is differ than that reported by[64]
who observed
that the clearance of ceftriaxone was significantly reduced in infected mice than in non
infected animals
The highest concentrations of ceftriaxone in milk are recorded 4 hours after each
intramuscular injection with a significant lower value in Salmonella typhimurium infected
goats than in normal goats This might be attributed to accumulation of drug in the inflammed
tissues[48]
This result is similar to those reported by[6559]
who found that milk concentrations
of gentamicin and cephradine were significantly lower in infected goats and cattle than in
normal ones respectively
The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the
non-ionic passive diffusion principle[66]
reported that most drug cross-lipid membranes by
passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly
influenced by the physicochemical properties of the drug[6768]
Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum
ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the
physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]
Milk
contains substantially more lipid and less protein than serum and is slightly more acidic
Therefore drugs which tend to concentrated in milk are weak bases with low serum protein
binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide
and aminothiazole also possesses an hydroxytriazinone group as new and additional
ionization center[70]
these compounds are sufficiently lipid- soluble to be able to penetrate
tissues
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The dose of ceftriaxone used in the present study induced therapeutically concentrations in
milk These concentrations suggested that ceftriaxone would be efficacious in treatment of
mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily
for 3-5 days
The study showed that the urine concentrations of ceftriaxone are greater than the concurrent
serum concentrations following intramuscular injection This observation is similar to those
reported in cows after cephapirin administrations[71]
In the present study urine concentrations of ceftriaxone increased with the repetition of
dosing This observation supported by[72]
after repeated intramuscular administrations of
ceftriaxone in healthy volunteeres
The mean peak urine concentrations of ceftriaxone were reached 2 hours after each
intramuscular injection The lower urine ceftriaxone concentrations in Salmonella
typhimurium infected goats than in normal goats might be attributed to the accumulation of
the drug in the inflamed tissues[48]
The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower
ratio in Salmonella typhimurium infected goats than in normal goats at different time of
sampling This indicates that glomerular filteration seemed to be the main pathway of
ceftriaxone elimination This observation supported by[59]
who found that the ratio between
cephradine clearance from blood of goats to creatinine clearance showed a marked decrease
in Escherichia-coli infected goats than in normal goats This indicated that glomerular
filteration seemed to be the main pathway of cephradine elimination with a limited rate of
tubular reabsorption
CONCLUSION
The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value
referred a better absorption of ceftriaxone from its site of intramuscular administration The
high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular
administrations suggested that ceftriaxone could be used for treatment of mastitis caused by
Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats
The high concentrations of ceftriaxone in urine after repeated intramuscular administrations
suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in
goats
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27 Abd-El-Aty AM Goudah A and Abo E S K (2001) Pharmacokinetics
intramuscular bioavailability and tissue residue profiles of ceftazidime in a rabbit
model Dtsch Tierarztl Wochenschr 108(4) 168-171
28 Gardner S Y and Papich M G (2001) Comparison of cefepime pharmacokinetics in
neonatal foals and adult dogs J Vet Pharmacol Therap 24(3) 187-192
29 Ismail M (2005a) Pharmacokinetics of cefepime administered by iv and im routes to
ewes J Vet Pharmacol Therap 28(6) 499-503
30 Patel U D Bhavsar S K and Thaker A M (2006) Pharmacokinetics and dosage
regimen of cefepime following single dose intravenous administration in calves Iran J
Pharmacol Therapeut 5(2) 127-130
31 El-Gendy AAM Tohamy MA and Ismail M (2007) Comparative pharmacokinetic
and renal clearance study of ceftiofur in cross breed friesian and buffalo calves BS Vet
Med J 17(1) 69-77
32 Joshi B and Kumar Sharma S (2009) The pharmacokinetics of cefepime in E coli
lipopolysaccharide induced febrile buffalo calves Veterinarski arhiv 79(6) 523-530
33 Tohamy MA (2008) Pharmacokinetics of ceftiofur sodium administered concomitantly
with dipyrone in healthy and feverish cows J Egypt Soc Pharmacol Exp Ther 29(2)
10-15
34 Rajput N Kumar V D and Sandhu HS (2011) Pharmacokinetics and dosage
regimen of cefpirome in febrile cross-bred calves Iran J Pharmacol Ther 10(1) 17-20
35 Abo-El- Sooud K and Tohamy MA (2011) Comparative pharmacokinetics and milk
concentrations of ceftazidime in healthy and mastitic goats Insight Pharmaceut Sci
1(1) 11-17
36 El-Hewaity M Abd El Latif A Soliman A and Aboubakr M (2014) Comparative
pharmacokinetics of cefquinome (Cobactan 25) following repeated intramuscular
administrations in sheep and goats J Vet Med Doi 949642 1-5
37 El-Sayed M G A El-Komy A A A El barawy A M and Ibrahim D M A (2015)
Pharmacokinetics and tissue residues of ceftiofur in normal and Escherichia coli infected
chickens J Phys Pharm Adv 5(3) 574-582
38 Datta B Mandal TK and Chakraborty A K (2003) Pharmacokinetics of cefotaxime
in goats with experimentally induced kidney damage Ind J pharmacol (35) 173-176
39 Guerrini HV English BP Filippich J L Schneider J and Bourne D W (1986)
The pharmacokinetics of cefotaxime in dog Vet Rec 119(4) 81-83
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
40 Atef M Ramadan A Afifi N A and Youssef S A (1990) pharmacokinetic profile
of cefotaxime in goat Res Vet Sci 49(1) 34-38
41 Satish K G Chaudhary RK Srivastiva AK and Garg BD (1990) Pharmacokintics
and dosage regemine of cephalexine in buffulo calves (Bubalis Bubalis following single
intravenous and intramusculer adminsteration Veterinary research commuincation 14
59-62
42 Goudah A (2008) Pharmacokinetic parameters of ceftriaxone after single intravenous
and intramuscular administration in camels (Camelus Dromedarius) Res Vet Sci Jun
84(3) 483-9
43 Sharma SK Srivastava AK and Deore DM (2006) Effect of Ecoli
lipopolysaccharides ndashinduced fever on disposition pattern of cefotaxime in buffalo calves
Veterinarski Arhiv 76(6) 537-545
44 Baggot JD (1977) Priniciple of pharmacokinetics In principle of drug disposition in
domestic animals The physiological Basis of veterinary Clinical Pharmacology 1st ed
WB Saunders Co Philadelphi PA 168-179
45 Karmaker UK Datta BK Patra PH Prashant M Suman S Sar TK Chakaborty
AK and mandal KT (2011) Disposition kinetics of ceftizoxime in healthy and mastitic
goats after intravenous adminsteration Pharmacologyonline 3 935-946
46 Ringger NC Pearson EG Gronwall R Kohlepp S J (1996) Pharmacokinetics of
ceftriaxone in healthy horses Equine Vet J Nov 28(6) 476-9
47 Prawez S Raina R Dimitrova D panka NK Ahanger AA Verma PK (2010) The
pharmacokinetics of cefipime in goats following single dose iv and im adminsteration
Turk j vet Anima Sci 34(5) 427-431
48 Baggot JD (1980) Distribution of antimicrobial agents in normal and diseased animals
JAVMA 19(76) 1085-1090
49 Haddad N S Pedersoli W M Ravis W R Fazeli M H and Carson Jr R L (1985)
Pharmacokinetics of gentamicin at steady-state in ponies serum urine and endometrial
concentrations Am J Vet Res 46(6) 1268-1271
50 Gupta JK Chaudhary RK and Dumka VK (2008) Pharmacokinetics after single
intramuscuker adminsrerarion and in-vitro binding plasma protein of cefoprazone in cross
bred calves Veterinaski Arhiv 78(5) 441-448
51 Al Taher AY (2010) Pharmacokinetics of cefquinome in camels J An Vet Ad 9(4)
848-852
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52 Rajput N Dumka V K and Sandhu HS (2012) Pharmacokinetics and in- vitro
plasma protein binding of cefpirome in cattle Veterinaski Arhiv 82(1) 1-9
53 RebueltoM Albarellos G Ambros L Kreil V Montoya L Bonafine R Otero P
Hallu R (2002) Pharmacokinetics of ceftriaxone administered by the intravenous
intramuscular or subcutaneous routes to dogs J Vet Pharmacol Ther Feb 25(1) 73-6
54 Patel RB Bhavsar SK Solanki PF Patel JH Varia RD Modi Falguni D and
Patel MD (2013) Pharmacokinetics of cefpirome following intravenous and
intramuscular administration in cow calves Sci Int 1(11) 371-374
55 Maradiya J J Goriya H V Bhavsar S K Patel U D and Thaker A M (2010)
Pharmacokinetics of ceftriaxone in calves Veterinarski arhiv 80(1) 1-9
56 Inges R MJ Fillastre J Godin M Leroy A and Humbert G (1982) The
Pharmacokinetics of cefotaxime and its metabolites in subjects with normal and impaired
renal function Clin Infect Dis (4) 379-391
57 Mcelroy D Ravis W R and Clark C H (1986) Pharmacokinetics of cefotaxime in
the domestic cats Am J Vet Res 47(1) 86-88
58 El-Sayed MG Atef M and El-Komy AA (1994) Disposition kinetic of cephradine in
normal and Escherichia coli infected goats Dtsch Tierarztl Wochenschr 101(2) 56-60
59 Soback S and Ziv G (1988) Pharmacokinetics and bioavailability of ceftriaxone
administered intravenously and intramuscularly to calves Am J Vet Res 49 535-538
60 Sharma S K and Srivastava A K (2003) Cefotaxime pharmacokinetics in male
buffalo calves following multiple dosing Veterinarski arhiv 73(4) 191-197
61 Abdulgafar O J Shaibu O B and Emmanuel U E (2011) Effect of Salmonella
typhymurium infection on the pharmacokinetics of ceftriaxone in sokoto red goats Niger
J Basic Applied Sci 19(1) 49-54
62 Ranjan R Birendra K R Amita R and Sanjeet K S (2011) Effect of Effect of E coli E
coli endotoxin induced fever on the pharmacokinetic profile and dosage regimen of
ceftriaxone in sheep (Ovis aries) Veterinarski arhiv 81(4) 423-432
63 Etuk EU and Onyeyili PA (2006) The effect of Salmonella infection on the plasma
kinetic of chloramphenicol in the sokoto red goats Inter J Pharmacol 2(1) 28-32
64 Wang E Bergeron Y and Bergeron MG (2005) Ceftriaxone pharmacokinetics in
interleukin-10-treated murine pneumococcal pneumonia J Antimicrob Chemother 55
721ndash726
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
65 El-Sayed MG Hatem ME and El-Komy AA (1989) Disposition kinetic of
gentamicin in normal and endometric cow using microbiological assay Dtsch Tierarztl
Wochenschr 96(8) 412-415
66 Aramyona JJ Mora J Fraile LJ Garcia MA Abadia AR and Breganate MA
(1996) Penetration of enrofloxacin and ciprofloxacin into breast milk and
pharmacokinetics of the drugs in lacating rabbits and neonatal offspring Am J Vet Res
57(4) 547-553
67 Rusmussen F (1966) Studies on the mammary excretion and absorbtion of drugs Vet
Rec (87) 14-18
68 Alkinson A and Begg E (1990) Prediction of drug distribution into human milk from
physicochemical characteristics Clin Pharmacokinet 18(2) 151-167
69 Kenneth F (1997) Drug distribution in human milk Aust Prescr 20(2) 35-40
70 Aleksić M Savić V Popović G Burić N and Kapetanović V (2005) Acidity
constants of cefetamet cefotaxime and ceftriaxone the effect of the substituent at C3
position J Pharm Biomed Anal 39(3-4) 752-756
71 Prades M Brown M P Gronwall R and Miles N S (1988) Pharmacokinetics of
sodium cephapirin in lactating dairy cows Am J Vet Res 49(11) 1888-1890
72 Holazo A A Patel I H Weinfeld R E Konikoff J J and Parsonnet M (1986)
Ceftriaxone pharmacokinetics following multiple intramuscular dosing Euro J Clin
Pharmacol 30(1) 109-112
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
INTRODUCTION
Ceftriaxone is a third-generation semi-synthetic bactericidal cephalosporin antibiotic
resistant to various types of bacterial β-lactamases It has excellent activity against gram
negative bacteria as well as a wide range of gram-positive and some anaerobic bacteria
including enterobacteriaceae Streptococcus pneumoniae Haemophilus inflfl uenzae
Pseudomonas aeruginosa and other non-enterococcal streptococci[123]
Like other
cephalosporin ceftriaxone bind to the penicillin-binding proteins (PBP) by covalent bond and
inactivate transpeptidase enzymes thereby inhibiting the peptidoglycan synthesis leading to
inhibition of the cell wall synthesis[4]
It has rapid absorption and wide distribution in tissues
as well as body fluids after parenteral administration in animals[5]
The drug thus seems to be
useful in the treatment of a variety of bacterial infections including meningitis septicemia
pyoderma colibacillosis surgical prophylaxis and urinary tract respiratory tract wound soft
tissue and joint infections[2]
Clinical pharmacology of ceftriaxone was investigated in human[6]
sheep[78]
goats[91011]
buffulo calves[1213]
calves[14]
domestic cats[15]
cross bred cow calves[16]
Little literature was
found concerning the pharmacokinetics of ceftriaxone in goats Thus the aim of present
work was undertaken to study the pharmacokinetic parameters of ceftriaxone after
intravenous and intramuscular injection in normal and experimentally Salmonella
typhimurium infected goats also the bioavailability of ceftriaxone was calculated after a
single intramuscular injection in normal goats
MATERIAL AND METHODS
Drug
Ceftriaxone is a member of third generation cephalosporins ceftriaxone sodium was used in
this study under the trade name (Cefaxonereg) It is available as glass vial containing 1000 mg
ceftriaxone it was produced by Pharco company Egypt
Experimental animals
Four clinically normal lactating baladi four experimentally infected goats and lactating goats
were used for each drug in this investigation The body weight and age of the tested goats
ranged from 20-26 kg and from 2 to 3 years old (for normal goats) and from 22 ndash 29 kg and
from 25 to 35 years old for experimentally infected goats They were housed in hygienic
stable fed on barseem drawa and concentrate Water was provided ad-libitum
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
Grouping of goats
Group (1)
It included 4 normal post-partum lactating goats Each goat was injected intravenously into
the left jugular vein ceftriaxone These goats were left for 15 days after the intravenous
injection to insure complete excretion of ceftriaxone from bodies of goats Then each goat
was injected intramuscularly into the gluteus medius muscle with the same dose of
ceftriaxone The aim of intramuscular injection to calculate the bioavailability of ceftriaxone
in normal goats
Group (2)
It included 4 normal post-partum lactating goats Each goat was injected intramuscularly into
the gluteus medius muscle with 20 mgkg bwt ceftriaxone for five consecutive days
Group (3)
It included 4 experimentally infected post-partum lactating goats with twenty four hours
peptone water culture of enterpathogen Salmonella typhimurium which were cultured on
nutrient agar plates for 24 hours then suspension of culture were collected by sterile saline
By opacity tube the required concentration of 2Χ109 micro-organismsml was obtained Each
of the four goats received orally a 10 ml suspension containing 2x109
organismml The
clinical symptoms of bacteraemia as fever and diarrhea appeared after 48-72 hours of
injection with Salmonella typhimurium suspension[17]
Each goat was injected
intramuscularly into the gluteus medius muscle with ceftriaxone per kilogram body weight
48 hours after experimental infection with samlonella Typhmurium for five consecutive days
Collection of samples
Blood samples
Blood samples were collected from right jugular vein following a single intravenous injection
of ceftriaxone in normal goats blood samples were collected after 5 min 10 min15 min 30
min 1 2 4 8 and 12 hours of administration Blood samples following the second third
fourth and fifth intramuscular doses were collected before and 10 min 15 min 050 1 2 4 8
and 12 hours post injection Blood samples taken from goats were allowed to clot and the
serum separated by centrifugation collected and divided in to two parts the first part was
used for assay of ceftriaxone and the second part was used for creatinine assay All serum
samples were stored at ndash 20degC until assay for ceftriaxone and creatinine
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
Urine samples
The urine sample was taken by using rubber balloon catheter (Folatex No 4158512) The
goats were catheterized and bladder was evacuated before each experiment Following
injection of ceftriaxone (single intravenous single intramuscular and repeated intramuscular
administration) in goats (normal and experimentally infected) urine samples were taken after
025 050 1 2 4 8 12 24 and 48 hours of administrations Urine sample which was taken
at 025 h was discarded Urine samples from goats of group (1) group (2) group (3) were
collected and divided into two parts the first part was used for assay of ceftriaxone and the
second part was used for creatinine assay All urine samples were stored at - 20degC until assay
for ceftriaxone After the end of each experiment the urinary bladder was irrigated with 15
milliliters potassium permanganate solution 1 5000 as antiseptic agent
Milk samples
The udder was completely evacuated before drug administration and milk samples were
collected by hand stripping from both teats Following injection of ceftriaxone (single
intravenous single intramuscular and repeated intramuscular administration) in goats (normal
and experimentally infected) milk samples were taken after 050 1 2 4 8 12 24 and 48
hours of administrations Milk sample which was taken at 025 h was discarded The udder of
each goat in all groups was completely evacuated before drug administration and after each
milk samples Milk samples from goats of all groups were allowed to clot (by mixing equal
volumes of milk and 25 trichloroacetic acid) and centrifuged The skim milk was collected
and stored at ndash 20degC until assay for ceftriaxone
Analytical Procedure
Assay of ceftriaxone
Ceftriaxone was assayed in goats serum distalled water and goats milk by microbiological
method using agar well diffusion method by using of Escherichia coli ATCC (American
type culture collection 25922) as tested microorganism which was obtained from
Microbiological Department Animal Health Institute Doky Giza Egypt)[18]
Concentrations of ceftriaxone in biological fluids were determined by modification of the
agar ndash plate diffusion method[19]
using Escherichia coli ATCC25922 as assay organism and
Muller Hinton agar media
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
Assay of samples
According to[20]
three plates were used for each sample Six pores were made three of them
were filled with reference concentration while the other three pores were filled with the
serum milk or urine samples in triplicate manner The plates were incubated at 37degC for 18
hours then the diameter of inhibitory zones were measured The diameter of inhibitory zones
of samples were corrected by using the zone diameter of the reference concentration in the
same manner as previously discussed either by addition or subtraction From the standard
curve the concentrations corresponding to the corrected values of the inhibitory zones were
obtained
Drug clearance
Clearance of the tested drug from the blood of goats was estimated according to the following
equation
Drug clearance10 kg b wt =
Drug concentration in urine (microgml) X rate of diuresis (mlmin) Body weight (Kg)
_________________________________________________________________
Drug concentration in serum (microgml) X 10
Assay of creatinine in serum and urine
Creatinine was assayed by[21]
and performed by kit manufactured by Diamond diagnostics
company
Creatinine clearance
The creatinine clearance (mlmin10 kgbwt) for goats was calculated by the following
equation
Creatinine clearance 10 kgbwt =
Creatinine concentration in urine (mgL) X rate of diuresis (mlmin) Body weight (Kg)
______________________________________________________________________
Creatinine concentration in serum (mgL) X 10
Pharmacokinetic analysis
The pharmacokinetic parameters were calculated by using Winonlin version 12 and other
parameters according to[2223]
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Statistical Analysis
The data were calculated as mean plusmn standard error All statistical analysis were carried out
according to[24]
using the scientific calculator CASIO fx 120
RESULTS
Following a single intravenous injection of 20 mg ceftriaxonekg bwt in normal goats
ceftriaxone could be detected therapeutically for 8 hours post intravenous injection The
serum concentration ndash time curve of ceftriaxone following intravenous injection showed that
the drug obeyed a two compartments open model (Figure 1) The disposition kinetics of
ceftriaxone following a single intravenous intramuscular injection were recorded in table (1)
Intramuscular injection of 20 mg ceftriaxone per kilogram body weight twice daily for five
consecutive days in normal and Salmonella typhimurium infected goats revealed a lower
significant serum ceftriaxone concentration after the first third fifth seventh ninth doses in
Salmonella typhimurium infected goats compared with normal goats The pharmacokinetic
parameters of ceftriaxone after repeated intramuscular injection in normal were compared to
those in Salmonella typhimurium infected goats (Table 2) and (Figure 2 amp 3)
The highest concentrations of ceftriaxone in milk were recorded 4 hours after each
intramuscular dose (Table 3) with a significant lower value in Salmonella typhimurium
infected goats compared with normal goats The calculated milkserum concentrations ratios
of ceftriaxone after repeated intramuscular injection (Table 4)
The amount of urine (mlmin) voided after repeated intramuscular injection of 20 mgkg bwt
Twice daily of ceftriaxone for five consecutive days in normal and experimentally
Salmonella typhimurium infected goats were recorded in table (5) The mean peak urine
concentrations of ceftriaxone (Table 6) were reached 2 hours after each intramuscular dose
with a lower significant concentration in Salmonella typhimurium infected goats compared
with normal goats Urineserum concentration ratios of ceftriaxone after repeated
intramuscular injection in normal and experimentally Salmonella typhimurium infected goats
were calculated and illustrated in table (7) Creatinine clearance (mlmin10 kg bwt)
expressing glomerular filtration rate from blood of goats was shown in table (8) The rate of
ceftriaxone clearance (mlmin10 kg bwt) from blood of goats was shown in table (9) The
ratio between ceftriaxone clearance and creatinine clearance was calculated and illustrated in
wwwwjppscom Vol 5 Issue 02 2016
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
table (10) The data revealed a significant lower ratio in Salmonella typhimurium infected
goats compared with normal goats after the third fifth seventh ninth doses
Table (1) Pharmacokinetics parameters of ceftriaxone (μgml) following a single
intravenous and intramuscuer injection of 20 mgkg bwt in normal goats (n=4)
Intramusculer_
(XplusmnS E)
Intravenous_
(XplusmnS E) Unit Parameters
-------- 1213 plusmn321321 microgml Cdeg
4360plusmn12343 61390 plusmn330 microgml A
43440plusmn43660 636 plusmn43316 h-1
α
43433plusmn3340 43340 plusmn43442 H (α) 43 T
43420plusmn43233 4333plusmn131 h-1
K12
43446plusmn43400 43409plusmn231 h-1
K21
-------- 43440plusmn431 lkg Vdss
4321plusmn6340 43636plusmn1303 microgml B
434446plusmn43419 43443plusmn43136 h-1
β
43141plusmn39340 43411plusmn331 H t05(β))
4344plusmn43401 434440plusmn43409 lkgh Cl tot
-------- 1136plusmn2111300 microgmlh AUMC
-------- 43303 plusmn0314 H MRT
9300plusmn2439 30plusmn034330 microgmlh AUC
3392plusmn63329 -------- F
43436plusmn4361 -------- h-1
K01
43420plusmn3346 -------- h-1
T05(k01)
4342plusmn330 -------- H Tmax(calc))
43021plusmn04343 -------- μgml Cmax(calc)
Cdeg Drug concentration in the serum at zero time immediately after a single intravenous
injection (μgml) A amp B Zero time plasma drug concentration intercepts of biphasic
intravenous disposition curve The coefficient B is based on the terminal exponential phase
(μgml) α amp β Hybrid rate constant of biphasic intravenous disposition curve values of α
and β are related to the slopes of distribution and elimination phase respectively of
biexponential drug disposition curve (h-1
) T05 (α) Distribution half ndash life (h) t05 (β)
Elimination half ndash life (h) K12 First ndash order transfer rate constant for drug distribution from
Central to peripheral compartment (h-1
) K21 First order transfer rate constant for drug
distribution from Peripheral to central compartment (h-1
) Vdss The apparent volume of
distribution which was calculated by steady ndash state method (mlkg) AUMC Area under
moment curve MRT Mean residence time AUC Total area under the serum drug
concentration versus time curve from t = 0 to t = α after administration of a single dose F
Bioavailability Cmax maximum drug concentration Tmax time of maximum observed
concentration in blood
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
Figure (1) Arthimatic plot of Serum concentrations of ceftriaxone (μgml) in normal
goats following a single intramuscular injection )diamsdiams( previously given the same doseby
a single intravenous injection () of 20 mg ceftriaxonekgbwt (n=4)
Figure (2) Semilogarthmic graph depicting the time course of ceftriaxone in serum of
normal goats following repeated ntramuscular injection of 20 mg ceftriaxonekgbwt
twice dialy for five consecutive days (n=4)
Figure (3) Semilogarthmic graph depicting the time course of ceftriaxone in serum of
experimentally Salmonella typhimurim infected goats following repeated ntramuscular
injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4) 3
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
Table (2) Pharmacokinetic parameters of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected
goats following repeated ntramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)
Dose
Unit
عىهParameters
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1269plusmn0073 7409plusmn121 1352plusmn0132 6373plusmn147 1410plusmn0243 5923plusmn126 1461plusmn0214 5430plusmn125 1424plusmn0172 7635plusmn176 gmlmicro A
0651plusmn0049 plusmn000843116 0720plusmn0008 plusmn00413300 0823plusmn0006 plusmn00263322 0848plusmn0025 plusmn00233323 0786plusmn0028 133plusmn0033 h-1 Α
106plusmn0008 330plusmn0015 0962plusmn0011 0392plusmn0007 0841plusmn0007 0567plusmn012 0818plusmn0024 0569plusmn0012 0885plusmn0030 plusmn00124322 H T05(α)
248plusmn0019 168plusmn0047 203plusmn0075 181plusmn0033 267plusmn0039 120plusmn0028 248plusmn0060 122plusmn0026 222plusmn0100 136plusmn0027 h-1 Kab
0278plusmn0002 0412plusmn0009 0342plusmn0012 0383plusmn0008 0252plusmn0009 0567plusmn0011 0279plusmn0005 00569plusmn0011 0314plusmn0014 0 510plusmn0012 H T05(ab)
0627plusmn0008 0378plusmn0007 0430plusmn0008 0402plusmn0008 0113plusmn00027 0424plusmn0009 0117plusmn0004 0394plusmn0008 0116plusmn0003 0239plusmn0005 h-1 K12
121plusmn0013 0962plusmn0022 141plusmn0021 130plusmn0023 0666plusmn0019 0651plusmn0013 0683plusmn0020 0660plusmn0013 0761plusmn0039 0998plusmn0023 h-1 K21
115plusmn0035 129plusmn0026 104plusmn0047 112plusmn0024 106plusmn0037 122plusmn0025 110plusmn0077 119plusmn0023 0910plusmn0032 123plusmn0023 H Tmax
4182plusmn0628 6108plusmn140 3440plusmn0363 5135plusmn0860 3117plusmn0965 4774plusmn0854 2713plusmn0781 4243plusmn0 870 2479plusmn0547 4065plusmn0825 gmlmicro Cmax
4944plusmn0820 7195plusmn142 4199plusmn0702 6511plusmn130 3190plusmn0688 5117plusmn113 3185plusmn0909 4709plusmn0990 3256plusmn0918 6329plusmn139 gmlmicro B
0164plusmn0003 0189plusmn00043 0181plusmn0002 0178plusmn0004 0181plusmn00035 0167plusmn0004 0214plusmn0009 0195plusmn0005 0249plusmn0918 0272plusmn0006 h-1 β
423plusmn0079 367plusmn0086 381plusmn0047 388plusmn0089 382plusmn0074 415plusmn0081 325plusmn0139 355plusmn0075 277plusmn0056 255plusmn0050 H T05β
0879plusmn0015 0429plusmn0009 109plusmn0004 0426plusmn0009 133plusmn0022 0503plusmn0011 154plusmn0064 0675plusmn0013 171plusmn0060 0693plusmn0014 Lkgh Cltot
28358plusmn215 40775plusmn808 21784plusmn0888 34259plusmn720 17860plusmn155 30705plusmn601 15281plusmn239 24135plusmn555 12175plusmn144 20292plusmn487 gmlhmicro AUC
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (3) Milk concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats
following repeated ntramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)
Dose Time of
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
197plusmn0205 200plusmn0408 125plusmn0104 155plusmn0132 0887plusmn0013 0885plusmn014 0500plusmn0040 074plusmn0012 ------------ ------ Before
200plusmn0408 22plusmn0108 197plusmn0205 200plusmn0408 155plusmn0132 197plusmn0205 100plusmn000 155plusmn0132 ----------- -------- 050
526plusmn0166 700plusmn0408 300plusmn0408 64plusmn0163 25plusmn0204 600plusmn0408 155plusmn0132 582plusmn0118 100plusmn000 520plusmn0166 1
640plusmn0163 900plusmn0408 582plusmn0118 792plusmn0114 582plusmn0118 755plusmn0221 275plusmn0061 700plusmn0408 200plusmn0408 691plusmn0176 2
900plusmn0408 1512plusmn0125 640plusmn0163 1475plusmn0322 640plusmn0163 1400plusmn0408 600plusmn0408 1352plusmn0205 526plusmn166 1225plusmn0595 4
wwwwjppscom Vol 5 Issue 02 2016
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
350plusmn0353 400plusmn0408 300plusmn0408 392plusmn0125 300plusmn0408 35plusmn0353 275plusmn006 300plusmn0408 155plusmn0132 275plusmn0061 6
300 plusmn0408 35plusmn0353 125plusmn0104 200plusmn0408 125plusmn0104 155plusmn01 0825plusmn0062 100plusmn000 0500plusmn0040 0887plusmn0013 8
200plusmn0408 22plusmn0108 100plusmn000 155plusmn0132 100plusmn000 125plusmn0104 0730plusmn002 0825plusmn0078 0422plusmn000 073plusmn0020 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (4) Milkserum concentrations ratios of ceftriaxone in normal and experimentally Salmonella typhimurim infected
goats following repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice daily for five consecutive days (n=4)
Dose Time of
a
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
0400plusmn0049 025plusmn0063 0307plusmn0026 021plusmn0019 0365plusmn00064 016plusmn0026 0232plusmn0016 0205plusmn0002 -------- helliphelliphelliphellip Before
0057plusmn0125 0042plusmn00025 0062plusmn00062 0042plusmn0010 0575plusmn00062 0055plusmn0006 0067plusmn0016 0049plusmn0005 --------- -------- 050
0127plusmn00062 0115plusmn00064 008plusmn0012 0117plusmn0004 0088plusmn00054 0122plusmn0008 008plusmn0017 0126plusmn0028 0039plusmn0005 0122plusmn0004 1
018plusmn0008 0185plusmn0010 021plusmn0004 017plusmn0004 0182plusmn0054 0179plusmn0006 0112plusmn00025 0193plusmn0012 0097plusmn0020 019plusmn0004 2
0357plusmn0020 0425plusmn0005 033plusmn0021 045plusmn0009 0285plusmn0082 0494plusmn0015 0395plusmn0016 0572plusmn001 0415plusmn0017 054plusmn0027 4
018plusmn0015 016plusmn0016 0207plusmn0022 0175plusmn0006 0257plusmn0037 0180plusmn0017 0272plusmn0015 0201plusmn003 0196plusmn0016 0222plusmn0002 6
0212plusmn0033 0212plusmn0020 0200plusmn0044 0122plusmn0024 0152plusmn0011 014plusmn0022 0122plusmn00062 0102plusmn0001 0107plusmn00094 0117plusmn0002 8
0372plusmn0042 025plusmn001 0325plusmn0027 0192plusmn0014 0265plusmn00064 0185plusmn0015 0272plusmn0125 0195plusmn0012 0252plusmn0032 0275plusmn0009 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
Table (5) The amount of urine (mlmin) voided in normal and experimentally Salmonella typhimurim infected goats following
repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)
Dose Time of a
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
plusmn00372344 126plusmn0034 130plusmn0030 130plusmn0028 118plusmn0066 118plusmn0067 108plusmn0013 108plusmn0008 ----------- -------- Before
0577plusmn0069 43494057plusmn 045plusmn0060 plusmn0064309 0312plusmn002 033plusmn0012 0340plusmn0024 033plusmn0012 0287plusmn0017 0272plusmn0014 050
0712plusmn0019 0692plusmn0014 068plusmn0081 0697plusmn0006 0672plusmn0011 0675plusmn 0009 0635plusmn0032 0655plusmn0010 0719plusmn0031 0697plusmn0015 1
0837plusmn0025 0787plusmn0021 0732plusmn0011 plusmn00054300 0715plusmn0011 0715plusmn002 0722plusmn0019 0702plusmn0018 0737plusmn0027 0762plusmn0041 2
0535plusmn0095 0507plusmn0021 0447plusmn0022 0452plusmn002 0402plusmn0075 0405plusmn0011 0400plusmn0057 0397plusmn0009 0380plusmn0004 038plusmn001 4
0437plusmn00094 0432plusmn0008 0400plusmn0010 0405plusmn0002 0380plusmn0007 plusmn00044319 0372plusmn0047 037plusmn 0007 0350plusmn0005 0365plusmn0006 6
0397plusmn0028 0410plusmn0008 0380plusmn0012 0395plusmn0009 0355plusmn0086 0352plusmn0007 0340plusmn0004 0345plusmn0005 0302plusmn0004 0335plusmn0005 8
0385plusmn001 0380plusmn0010 0385plusmn00064 0380plusmn0008 0365plusmn0064 0367plusmn0004 0362plusmn0086 0372plusmn0106 0327plusmn0006 0362plusmn0016 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (6) Urine concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats
following repeated intramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)
Dose Time of a
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1125plusmn150 1125plusmn15 735plusmn287 81plusmn324 183plusmn03 555plusmn798 37plusmn0811 1815plusmn43290 -------------- ------ Before
2415plusmn357 2625plusmn374 1695plusmn788 249plusmn574 10575plusmn64 2415plusmn357 5400plusmn273 2085plusmn991 102plusmn160 168plusmn547 050
26025plusmn787 2923plusmn479 22425plusmn1225 2805plusmn35 1695plusmn618 2705plusmn471 10200plusmn547 2415plusmn357 6975plusmn225 22425plusmn894 1
29295plusmn765 3012plusmn346 28575plusmn738 2964plusmn415 2355plusmn259 2923plusmn479 1635plusmn561 2645plusmn917 102plusmn547 24825plusmn616 2
23475plusmn430 2482plusmn616 23475plusmn1564 2415plusmn357 1695plusmn788 198plusmn848 8475plusmn309 1515plusmn708 60plusmn212 1185plusmn45 4
1905plusmn45 2355plusmn259 153plusmn519 1935plusmn960 114plusmn948 159plusmn173 6675plusmn309 1215plusmn45 1312plusmn0552 855plusmn193 6
153plusmn1024 1965plusmn135 1335plusmn1229 150plusmn34 735plusmn295 1365plusmn665 6181plusmn339 72plusmn244 907plusmn0951 5025plusmn143 8
135plusmn519 120plusmn346 11725plusmn1551 96plusmn874 525plusmn295 75plusmn173 153plusmn130 39plusmn212 3735plusmn0458 13125plusmn0552 12
Between normal and diseased
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (7) Urineserum concentrations ratios of ceftriaxone following repeated ntramuscular injection of 20 mg
ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats
(n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
229plusmn 163 1448plusmn0743 1885plusmn159 1125plusmn0484 533plusmn0260 1050plusmn358 175plusmn0380 4146plusmn116 ------- ------ Before
741plusmn0063 plusmn01553 58plusmn0242 plusmn0149390 422plusmn0206 683plusmn0106 245plusmn0092 667plusmn0306 0510plusmn0081 559plusmn0181 050
651plusmn0243 plusmn0065031 637plusmn0373 plusmn014431 565plusmn0243 plusmn0085300 360plusmn0303 plusmn0110312 279plusmn0121 534plusmn0248 1
836plusmn0150 plusmn00476322 862plusmn0180 plusmn010463 942plusmn0166 plusmn0130631 217plusmn0303 727plusmn0256 508plusmn0186 plusmn01680340 2
939plusmn0235 plusmn01580344 1006plusmn0710 plusmn00750310 999plusmn0542 plusmn02850344 565plusmn0223 641plusmn0241 48plusmn0164 plusmn014834 4
1005plusmn0418 2plusmn018813 1097plusmn0641 plusmn03979300 993plusmn0921 plusmn0252931 619plusmn0483 plusmn0362933 167plusmn0101 642plusmn0644 6
1091plusmn0649 plusmn075332339 1171plusmn0980 995plusmn0415 925plusmn0593 plusmn05593433 886plusmn0408 plusmn02510311 2055plusmn0311 plusmn02046310 8
2392plusmn129 plusmn032731396 1794plusmn0228 1222plusmn124 1418plusmn109 plusmn026733336 580plusmn0397 plusmn03951326 227plusmn0452 plusmn02740316 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (8) Creatinine clearance (mlmin10kgbwt) following repeated intramuscular injection of 20 mg ceftriaxonekgbwt
twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats (n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1115plusmn0703 2265plusmn167 481plusmn0409 672plusmn0817 669plusmn0672 1202plusmn0777 695plusmn0634 1724plusmn179 ----------- ------ Before
0703plusmn0091 147plusmn0305 0718plusmn0141 251plusmn0707 0547plusmn0055 0699plusmn0092 0802plusmn0099 103plusmn0106 295plusmn0124 0458plusmn0037 050
101plusmn0075 161plusmn0093 131plusmn0099 264plusmn0217 161plusmn0146 373plusmn0499 247plusmn0110 4755plusmn0582 214plusmn0234 103plusmn0166 1
157plusmn0198 387plusmn0340 173plusmn0501 267plusmn0217 187plusmn0563 287plusmn0499 451plusmn0223 972plusmn105 263plusmn0399 169plusmn0454 2
wwwwjppscom Vol 5 Issue 02 2016
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
184plusmn0095 346plusmn0444 173plusmn0501 436plusmn0599 383plusmn0299 682plusmn0584 328plusmn0253 119plusmn153 123plusmn0057 292plusmn0742 4
221plusmn0242 411plusmn0661 241plusmn0186 663plusmn0584 308plusmn0234 422plusmn0314 353plusmn0393 548plusmn0901 105plusmn0057 264plusmn0294 6
261plusmn0295 476plusmn0339 319plusmn0273 753plusmn0676 106plusmn0207 0773plusmn0049 228plusmn0175 456plusmn0340 206plusmn0160 404plusmn0419 8
310plusmn0218 409plusmn0434 3264plusmn0153 669plusmn0476 209plusmn0189 235plusmn0337 217plusmn0143 377plusmn0342 240plusmn0218 6055plusmn0176 12
Between normal and diseased
Plt 005 Plt001 Plt0001
Table (9) Ceftriaxone clearance (mlmin10kgbwt following repeated intramuscular injection of 20 mg ceftriaxone kgbwt
twice in normal and experimentally Salmonella typhimurim infected goats (n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1048plusmn121 0557plusmn684 895plusmn113 0547plusmn560 238plusmn0222 103plusmn 480 0668plusmn0157 0173plusmn216 -------- ----------- Before
156plusmn0251 43204plusmn3322 0936plusmn0162 43211plusmn3334 0473plusmn0037 43469plusmn43964 0300plusmn0028 43341plusmn080 0190plusmn0137 43400plusmn43642 050
166plusmn0079 43323plusmn3311 157plusmn0178 43419plusmn3301 137plusmn0115 43311plusmn33022 0883plusmn0054 43341plusmn 133 0616plusmn0153 43120plusmn3301 1
254plusmn0272 43361plusmn3391 222plusmn0093 4331plusmn3390 243plusmn0180 43209plusmn3309 183plusmn0149 43310plusmn2340 128plusmn0153 43312plusmn3390 2
181plusmn0136 43339plusmn3316 161plusmn0129 433plusmn3329 144plusmn0100 43412plusmn3349 0821plusmn0072 0063plusmn0977 0654plusmn0065 43400plusmn4306 4
160plusmn0177 43393plusmn336 152plusmn0200 43416plusmn331 135plusmn0118 4332plusmn3322 0897plusmn0052 43304plusmn3330 0212plusmn0022 43460plusmn43112 6
153plusmn0049 43291plusmn234 163plusmn0242 43346plusmn3300 0891plusmn0272 43306plusmn3310 108plusmn0071 43416plusmn04310 0229plusmn0046 43490plusmn43916 8
340plusmn0522 43214plusmn2341 249plusmn0150 43112plusmn3393 186plusmn0159 43320plusmn336 0773plusmn0094 43390plusmn 134 0264plusmn0043 43400plusmn 54369 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
Table (10) Ceftriaxone clearancecreatinine clearance following repeated ntramuscular injection of 20 mg
ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats
(n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
0934plusmn0083 0305plusmn0013 183plusmn0116 0864plusmn0098 0358plusmn0018 0279plusmn0047 0099plusmn0020 0127plusmn0001 ------- ----------- Before
220plusmn0115 0819plusmn0044 131plusmn00414 0458plusmn0029 0876plusmn0063 126plusmn0068 0361plusmn0011 0813plusmn0031 0018plusmn0003 108plusmn0062 050
164plusmn0078 0818plusmn0029 118plusmn0068 0546plusmn0027 0858plusmn0052 0407plusmn0041 0331plusmn0009 0287plusmn0025 0324plusmn0011 0909plusmn0187 1
161plusmn0044 0488plusmn0005 232plusmn128 0329plusmn0027 169plusmn0464 0686plusmn0050 0409plusmn0020 0220plusmn0029 0512plusmn0077 266plusmn177 2
0933plusmn0024 0394plusmn0005 0948plusmn0062 0296plusmn0007 0381plusmn0027 0160plusmn0008 0235plusmn0014 0083plusmn0006 0528plusmn0028 0362plusmn0041 4
0726plusmn0018 0411plusmn0028 0639plusmn0066 0204plusmn0006 0446plusmn0034 0286plusmn0008 0238plusmn0019 0214plusmn0006 020plusmn0013 0382plusmn0028 6
0609plusmn0072 0425plusmn0036 0508plusmn0052 0192plusmn0009 0524plusmn0146 174plusmn0083 0477plusmn0015 0213plusmn00018 0109plusmn0185 0222plusmn0006 8
108plusmn0128 0496plusmn0012 0942plusmn0004 0265plusmn0030 0891plusmn0056 0706plusmn0103 0351plusmn0022 0354plusmn0018 0111plusmn0021 0098plusmn0018 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
DISCUSSION
In the present investigation intravenous injection of 20 mg ceftriaxonekgbwt in normal goats the drug showed high serum level
(92plusmn 0408 μgml) at 5 minutes post-injection then its concentration was decreased gradually till reached its minimum level (18
plusmn0816μgml) at 8hours post-injection
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
In the present investigation the intravenous injection of 20 mg ceftriaxonekgbwt In normal
goats showed that the drug disposition best fitted a two-compartments- open model a
compartment of plasma and rapid equilibrating tissues and a deeper slower compartment
The obtained result is consistent with those reported for ceftriaxone in lactating goats[9]
lactating ewe[25]
domestic cat[15]
calves[26]
and patanwadi sheep[8]
Also this phenomenon is
in agreement with those reported for other cephalosporines as ceftazidime in a rabbit[27]
cefepime in dog and neonatal foals[28]
ewes[29]
ceftriaxone in goats[9]
cefipime in calves[30]
ceftiofur in cross-bred friesian cattle[31]
cefipime in calves[32]
ceftiofur in cows[33]
cefpirome
in cross-bred calves[3]
cefazidime in goats[35]
and cefquinome in sheep and goats[36]
cefipime
in chickens[37]
Ceftriaxone was distributed after intravenous injection with a distribution phase (α) equal to
656 per hour with a short distribution half ndash life [t05 (α)] equal to 0104 hour The shorter
distribution half-life of ceftriaxone in goats suggested the rapid distribution of the drug in
body tissue and fluid and that nearly similar to that recorded for ceftriaxone in lactating
goats(012 hour)[9]
for ceftriaxone in lactating ewes (0152 hour)[2]
and for ceftriaxone in
calves( 013hour)[26]
The rapid distribution of ceftriaxone in goats is supported by high rate constant of transfer of
the drug from central to peripheral compartment [K12 = 353 h-1
] as compared to the rate
constant of transfer of the drug from peripheral to central compartment [K21= 295 h-1
] This
value is nearly similar to those reported for cefotaxime in goats (K21=327 h-1
)[38]
On contrast
this value was higher than those recorded for ceftriaxone in lactating goats (K21=143 h-1
)[9]
in
lactating ewes (K21=125 h-1
)[25]
and in domestic cats (K21=154 h-1
)[15]
The apparent volume of distribution of ceftriaxone was (0355plusmn0004LKg) this value is
nearly similar to that recorded for cefaronide in sheep(039 LKg)[7]
cefotaxime in dog (048
lkg)[39]
in goat (051 lkg)
[40] for caphalexin in buffalo calves (041 Lkg)
[41] for cefipime in
ewes and calves (032 lkg) (043Lkg)[29]
and[30]
respectively For ceftriaxone in domestic
cats (057Lkg)[15]
in camel (032Lkg)[42]
On the other hand this result is differ than that
reported for cefotaxime in buffalo calves (117Lkg)[43]
High value of the volume of
distribution suggested extensive penetration power Drug with volume of distribution greater
than one literkilogram indicated wide distribution or extensive tissue binding or both[44]
The
apparent volume of distribution in the present study indicated moderate tissue penetrating
power This result agreed with[15]
for ceftriaxone in domestic cats
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
Ceftriaxone is eliminated in the current study following a single intravenous injection with
elimination half ndashlife [t 05(β)] equal to 519 hours This observation is nearly agreed with the
data recorded for ceftizoxime in goats (624hours)[45]
On contrast this value was longer than
that reported for ceftriaxone in lactating ewe (175hours)[25]
for cefaronide in sheep (17
hours)[7]
For cephalexin in buffulo calves (216hours)[41]
for ceftriaxone in healthy horse
(162hours)[46]
also this value is longer than that recorded for ceftriaxone in lactating goats
(144hours)[9]
for cefipime in goats (186hours)[47]
The rate of total body clearance of ceftriaxone following a single intravenous injection is
0048 lkgh which equal to data reported for ceftizoxime in lactating goats (005Lkgh)[45]
On contrast this value is lower than that reported for ceftriaxone in buffulo calves lactating
goats buffulo calves (Bubalus bubalis) goats (capra hircus) patanwadi sheep (026 Lkgh)
(395 Lkgh) (440 Lkgh) (450 Lkgh) (391 Lkgh)[12913118]
respectively
The variation in total body clearance might be attributed to specific interspecies variation
handling of the drug method used healthy status of the animal[48]
The difference between values calculated for pharmacokinetic parameters may be attributed
to animal species the drug formulation employed the age the size or sex o l lf the animal
or even inter individual variation and also due to method of analysis of the drug[49]
Following a single intramuscular injection of 20 mg ceftriaxonekg bwt In normal goats the
drug reached its peak serum concentrations after one hour of injection with value
of(41μgml) Ceftriaxone could be detected in serum in a therapeutic level (263μgml) at 12
hours post-injection The reported peak serum concentrations neerly similar to that reported
for cephalexin in buffulo calves (457 microgml)[41]
These results is differed than those reported
for ceftriaxone in cross breed calves (188 microgml at 30 min[16]
in Kangro breed of goats
(Capra Hircus) (2640 microgml at 20 min[10][50]
found after intramuscular administration of
ceforazone peak plasma concentration was (976 microgml) at 45min This result was also higher
than that recorded for ceftriaxone in buffalo calves (158 microgml)[13]
The calculated maximum serum concentration (Cmax) is (40015 microgml) at maximum time
(tmax) of 157 hours The reported (Cmax) agreed with the data reported for cefipime in goats
(4932 microgml[47]
The reported maximum serum concentration (Cmax) is higher than that
reported for ceftriaxone in lactating goats(236 microgml)[9]
in lactating ewes (1722 microgml[25]
in
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
goats (2151 microgml)[11]
for cefquinome in camels (123 microgml)[51]
for ceftriaxone in calves
(1534 microgml)[26]
in patanwadi sheep (1553 microgml)[8]
for cefpirome in cattle (101 microgml)[52]
And for ceftiofur in chickens (2594 μgml)[37]
On the other hand the result was lower than
that reported by[6]
who observed the maximum serum concentration (Cmax) of ceftriaxone in
human after ntramuscular administration was (805 microgml) also it was lower than that
reported for ceftriaxone in dog (11510 microgml)[53]
in domestic cats (5440 microgml)[15]
and for
ceftazoxime in goats (8878 microgml)[45]
The reported [tmax] is neerly similar to that reported for ceftriaxone (104hours)in lactating
ewes by[25]
On contrast it is longer than those reported for ceftriaxone in dogs
(129hours)[53]
for ceftriaxone in lactating goats (07hours)[9]
also the result was longer than
that reported for ceftriaxone in domestic cats (033hours)[15]
in buffulo calves (05 hours)[13]
and for cefpirome in cattle (075hours)[52]
The reported [tmax] is shorter than those reported
for cefquinome in camels (425hours)[51]
in sheep and goats (261 and 262 hours)[36]
and for
ceftiofur in chickens (251 hours)[37]
The elimination half life [t05(β)]
following a single intramuscular administration was 1804 hours This value is nearly agreed
with that recorded for cefquinomein camels (1024hours)[52]
On contrast this result is longer
than that reported for cephalexin in buffalo calves (243hours)[41]
for ceftriaxone in lactating
ewes (177hours)[25]
in buffalo calves (438hours)[13]
in goats (203 hours)[11]
and for
cefipime in goats (165 hours)[47]
The rate of total body clearance of ceftriaxone following a single intramuscular injection is
0043lkgh This value was lower than that reported for ceftriaxone in buffulo calves
(401Lkgh)[13]
in goats (304 Lkgh)[11]
and in sheep (222 Lkgh)[8]
Bioavailability is the fraction of the drug administered by non vascular rout that gains
accesses to the systemic circulation The obtained result revealed that the calculated systemic
bioavailability percent was 6128 It is equal to that recorded for cefpirome in cow calves
(61)[54]
It is nearly equal to that recorded for ceftriaxone in sheep (64)[8]
On the other
hand this value is higher than those recorded for cefperazone in crossbred calves (481)[50]
for ceftriaxone in goats (59)[11]
in calves (47)[55]
On contrast this value is lower than
those reported for cefotaxime in two cats 982 and 93)[57]
for cephradine in goats
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
(739)[58]
for ceftazidime in a rabbit (966)[27]
for ceftriaxone in lactating goats (85)[9]
in lactating ewes (836)[25]
in domestic cats 8572[15]
for cefipime in goats 8645[47]
for ceftriaxone in buffulo calves 702[13]
and for ceftiofur in chickens 8890[37]
Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium
infected goats twics dialy for five days revealed that the drug could be detected in a
therapeutic level for 12hours following repeated intramuscular administrations and exceeded
the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]
The relative higher serum concentrations of ceftriaxone after the last dose compared to the
first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12
hours intervals for five consecutive days These observations agreed with data reported by[36]
on comparing the data of serum levels of repeated intramuscular injections with first
intramuscular injection it was revealed that repeated intramuscular injections of cefquinome
have cumulative effect in both species sheep and goats
The obtained result is inconsistent with that reported by[56]
who found thatwhen cefotaxime
was administered repetitively in patients the ratio of maximal serum levels after the last dose
to those after the first dose demonstrated minimal accumulation of intact drug and by[60]
who
found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in
buffalo calves
The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium
infected goats are significantly lower than those in normal goats following repeated
intramuscular injection These lower blood concentrations in Salmonella typhimurium
infected goats might be attributed to the higher penetrating power of ceftriaxone to the
diseased tissues[48]
This phenomenon is similar to data recorded by[61]
who suggested that
Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of
ceftriaxone These alterations might be due to fever and inflammation induced by
infections[59]
proved that the serum concentrations of cephradine following intramuscular
administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after
each intramuscular dose with a lower significant values recorded in Escherichia-coli infected
goats than in normal goatsAlso similer to that reported by[62]
who observed that the
maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
in comparison to normal sheepOn contrast[43]
reported that peak plasma level of cefotaxime
in febrile buffalo calves was higher than healthy buffalo calves
In this study the total body clearance (CLtot) in normal goats are significantly lower than in
Salmonella typhimurium infected goats This result supported by[61]
and[63]
fever and
inflammation are cardinal features in bacterial infection which may in turn caused an
increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all
these could lead to increased in the rate at which the drug was delivered to both organs which
were important sites of drug excretion This might somewhat explain the increase in the total
body clearance in infected goats This result is differ than that reported by[64]
who observed
that the clearance of ceftriaxone was significantly reduced in infected mice than in non
infected animals
The highest concentrations of ceftriaxone in milk are recorded 4 hours after each
intramuscular injection with a significant lower value in Salmonella typhimurium infected
goats than in normal goats This might be attributed to accumulation of drug in the inflammed
tissues[48]
This result is similar to those reported by[6559]
who found that milk concentrations
of gentamicin and cephradine were significantly lower in infected goats and cattle than in
normal ones respectively
The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the
non-ionic passive diffusion principle[66]
reported that most drug cross-lipid membranes by
passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly
influenced by the physicochemical properties of the drug[6768]
Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum
ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the
physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]
Milk
contains substantially more lipid and less protein than serum and is slightly more acidic
Therefore drugs which tend to concentrated in milk are weak bases with low serum protein
binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide
and aminothiazole also possesses an hydroxytriazinone group as new and additional
ionization center[70]
these compounds are sufficiently lipid- soluble to be able to penetrate
tissues
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
The dose of ceftriaxone used in the present study induced therapeutically concentrations in
milk These concentrations suggested that ceftriaxone would be efficacious in treatment of
mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily
for 3-5 days
The study showed that the urine concentrations of ceftriaxone are greater than the concurrent
serum concentrations following intramuscular injection This observation is similar to those
reported in cows after cephapirin administrations[71]
In the present study urine concentrations of ceftriaxone increased with the repetition of
dosing This observation supported by[72]
after repeated intramuscular administrations of
ceftriaxone in healthy volunteeres
The mean peak urine concentrations of ceftriaxone were reached 2 hours after each
intramuscular injection The lower urine ceftriaxone concentrations in Salmonella
typhimurium infected goats than in normal goats might be attributed to the accumulation of
the drug in the inflamed tissues[48]
The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower
ratio in Salmonella typhimurium infected goats than in normal goats at different time of
sampling This indicates that glomerular filteration seemed to be the main pathway of
ceftriaxone elimination This observation supported by[59]
who found that the ratio between
cephradine clearance from blood of goats to creatinine clearance showed a marked decrease
in Escherichia-coli infected goats than in normal goats This indicated that glomerular
filteration seemed to be the main pathway of cephradine elimination with a limited rate of
tubular reabsorption
CONCLUSION
The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value
referred a better absorption of ceftriaxone from its site of intramuscular administration The
high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular
administrations suggested that ceftriaxone could be used for treatment of mastitis caused by
Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats
The high concentrations of ceftriaxone in urine after repeated intramuscular administrations
suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in
goats
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25 Goudah A Shin HC Shim JH Abd El-Aty AM (2006) Characterization of the
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26 Jayesh J M Harshad V G Shailesh K B Urvesh D P and Aswin M T (2010)
Pharmacokinetics of ceftriaxone in calves Veterinarski arshiv 80(1) 1-9
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1455
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27 Abd-El-Aty AM Goudah A and Abo E S K (2001) Pharmacokinetics
intramuscular bioavailability and tissue residue profiles of ceftazidime in a rabbit
model Dtsch Tierarztl Wochenschr 108(4) 168-171
28 Gardner S Y and Papich M G (2001) Comparison of cefepime pharmacokinetics in
neonatal foals and adult dogs J Vet Pharmacol Therap 24(3) 187-192
29 Ismail M (2005a) Pharmacokinetics of cefepime administered by iv and im routes to
ewes J Vet Pharmacol Therap 28(6) 499-503
30 Patel U D Bhavsar S K and Thaker A M (2006) Pharmacokinetics and dosage
regimen of cefepime following single dose intravenous administration in calves Iran J
Pharmacol Therapeut 5(2) 127-130
31 El-Gendy AAM Tohamy MA and Ismail M (2007) Comparative pharmacokinetic
and renal clearance study of ceftiofur in cross breed friesian and buffalo calves BS Vet
Med J 17(1) 69-77
32 Joshi B and Kumar Sharma S (2009) The pharmacokinetics of cefepime in E coli
lipopolysaccharide induced febrile buffalo calves Veterinarski arhiv 79(6) 523-530
33 Tohamy MA (2008) Pharmacokinetics of ceftiofur sodium administered concomitantly
with dipyrone in healthy and feverish cows J Egypt Soc Pharmacol Exp Ther 29(2)
10-15
34 Rajput N Kumar V D and Sandhu HS (2011) Pharmacokinetics and dosage
regimen of cefpirome in febrile cross-bred calves Iran J Pharmacol Ther 10(1) 17-20
35 Abo-El- Sooud K and Tohamy MA (2011) Comparative pharmacokinetics and milk
concentrations of ceftazidime in healthy and mastitic goats Insight Pharmaceut Sci
1(1) 11-17
36 El-Hewaity M Abd El Latif A Soliman A and Aboubakr M (2014) Comparative
pharmacokinetics of cefquinome (Cobactan 25) following repeated intramuscular
administrations in sheep and goats J Vet Med Doi 949642 1-5
37 El-Sayed M G A El-Komy A A A El barawy A M and Ibrahim D M A (2015)
Pharmacokinetics and tissue residues of ceftiofur in normal and Escherichia coli infected
chickens J Phys Pharm Adv 5(3) 574-582
38 Datta B Mandal TK and Chakraborty A K (2003) Pharmacokinetics of cefotaxime
in goats with experimentally induced kidney damage Ind J pharmacol (35) 173-176
39 Guerrini HV English BP Filippich J L Schneider J and Bourne D W (1986)
The pharmacokinetics of cefotaxime in dog Vet Rec 119(4) 81-83
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40 Atef M Ramadan A Afifi N A and Youssef S A (1990) pharmacokinetic profile
of cefotaxime in goat Res Vet Sci 49(1) 34-38
41 Satish K G Chaudhary RK Srivastiva AK and Garg BD (1990) Pharmacokintics
and dosage regemine of cephalexine in buffulo calves (Bubalis Bubalis following single
intravenous and intramusculer adminsteration Veterinary research commuincation 14
59-62
42 Goudah A (2008) Pharmacokinetic parameters of ceftriaxone after single intravenous
and intramuscular administration in camels (Camelus Dromedarius) Res Vet Sci Jun
84(3) 483-9
43 Sharma SK Srivastava AK and Deore DM (2006) Effect of Ecoli
lipopolysaccharides ndashinduced fever on disposition pattern of cefotaxime in buffalo calves
Veterinarski Arhiv 76(6) 537-545
44 Baggot JD (1977) Priniciple of pharmacokinetics In principle of drug disposition in
domestic animals The physiological Basis of veterinary Clinical Pharmacology 1st ed
WB Saunders Co Philadelphi PA 168-179
45 Karmaker UK Datta BK Patra PH Prashant M Suman S Sar TK Chakaborty
AK and mandal KT (2011) Disposition kinetics of ceftizoxime in healthy and mastitic
goats after intravenous adminsteration Pharmacologyonline 3 935-946
46 Ringger NC Pearson EG Gronwall R Kohlepp S J (1996) Pharmacokinetics of
ceftriaxone in healthy horses Equine Vet J Nov 28(6) 476-9
47 Prawez S Raina R Dimitrova D panka NK Ahanger AA Verma PK (2010) The
pharmacokinetics of cefipime in goats following single dose iv and im adminsteration
Turk j vet Anima Sci 34(5) 427-431
48 Baggot JD (1980) Distribution of antimicrobial agents in normal and diseased animals
JAVMA 19(76) 1085-1090
49 Haddad N S Pedersoli W M Ravis W R Fazeli M H and Carson Jr R L (1985)
Pharmacokinetics of gentamicin at steady-state in ponies serum urine and endometrial
concentrations Am J Vet Res 46(6) 1268-1271
50 Gupta JK Chaudhary RK and Dumka VK (2008) Pharmacokinetics after single
intramuscuker adminsrerarion and in-vitro binding plasma protein of cefoprazone in cross
bred calves Veterinaski Arhiv 78(5) 441-448
51 Al Taher AY (2010) Pharmacokinetics of cefquinome in camels J An Vet Ad 9(4)
848-852
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52 Rajput N Dumka V K and Sandhu HS (2012) Pharmacokinetics and in- vitro
plasma protein binding of cefpirome in cattle Veterinaski Arhiv 82(1) 1-9
53 RebueltoM Albarellos G Ambros L Kreil V Montoya L Bonafine R Otero P
Hallu R (2002) Pharmacokinetics of ceftriaxone administered by the intravenous
intramuscular or subcutaneous routes to dogs J Vet Pharmacol Ther Feb 25(1) 73-6
54 Patel RB Bhavsar SK Solanki PF Patel JH Varia RD Modi Falguni D and
Patel MD (2013) Pharmacokinetics of cefpirome following intravenous and
intramuscular administration in cow calves Sci Int 1(11) 371-374
55 Maradiya J J Goriya H V Bhavsar S K Patel U D and Thaker A M (2010)
Pharmacokinetics of ceftriaxone in calves Veterinarski arhiv 80(1) 1-9
56 Inges R MJ Fillastre J Godin M Leroy A and Humbert G (1982) The
Pharmacokinetics of cefotaxime and its metabolites in subjects with normal and impaired
renal function Clin Infect Dis (4) 379-391
57 Mcelroy D Ravis W R and Clark C H (1986) Pharmacokinetics of cefotaxime in
the domestic cats Am J Vet Res 47(1) 86-88
58 El-Sayed MG Atef M and El-Komy AA (1994) Disposition kinetic of cephradine in
normal and Escherichia coli infected goats Dtsch Tierarztl Wochenschr 101(2) 56-60
59 Soback S and Ziv G (1988) Pharmacokinetics and bioavailability of ceftriaxone
administered intravenously and intramuscularly to calves Am J Vet Res 49 535-538
60 Sharma S K and Srivastava A K (2003) Cefotaxime pharmacokinetics in male
buffalo calves following multiple dosing Veterinarski arhiv 73(4) 191-197
61 Abdulgafar O J Shaibu O B and Emmanuel U E (2011) Effect of Salmonella
typhymurium infection on the pharmacokinetics of ceftriaxone in sokoto red goats Niger
J Basic Applied Sci 19(1) 49-54
62 Ranjan R Birendra K R Amita R and Sanjeet K S (2011) Effect of Effect of E coli E
coli endotoxin induced fever on the pharmacokinetic profile and dosage regimen of
ceftriaxone in sheep (Ovis aries) Veterinarski arhiv 81(4) 423-432
63 Etuk EU and Onyeyili PA (2006) The effect of Salmonella infection on the plasma
kinetic of chloramphenicol in the sokoto red goats Inter J Pharmacol 2(1) 28-32
64 Wang E Bergeron Y and Bergeron MG (2005) Ceftriaxone pharmacokinetics in
interleukin-10-treated murine pneumococcal pneumonia J Antimicrob Chemother 55
721ndash726
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
65 El-Sayed MG Hatem ME and El-Komy AA (1989) Disposition kinetic of
gentamicin in normal and endometric cow using microbiological assay Dtsch Tierarztl
Wochenschr 96(8) 412-415
66 Aramyona JJ Mora J Fraile LJ Garcia MA Abadia AR and Breganate MA
(1996) Penetration of enrofloxacin and ciprofloxacin into breast milk and
pharmacokinetics of the drugs in lacating rabbits and neonatal offspring Am J Vet Res
57(4) 547-553
67 Rusmussen F (1966) Studies on the mammary excretion and absorbtion of drugs Vet
Rec (87) 14-18
68 Alkinson A and Begg E (1990) Prediction of drug distribution into human milk from
physicochemical characteristics Clin Pharmacokinet 18(2) 151-167
69 Kenneth F (1997) Drug distribution in human milk Aust Prescr 20(2) 35-40
70 Aleksić M Savić V Popović G Burić N and Kapetanović V (2005) Acidity
constants of cefetamet cefotaxime and ceftriaxone the effect of the substituent at C3
position J Pharm Biomed Anal 39(3-4) 752-756
71 Prades M Brown M P Gronwall R and Miles N S (1988) Pharmacokinetics of
sodium cephapirin in lactating dairy cows Am J Vet Res 49(11) 1888-1890
72 Holazo A A Patel I H Weinfeld R E Konikoff J J and Parsonnet M (1986)
Ceftriaxone pharmacokinetics following multiple intramuscular dosing Euro J Clin
Pharmacol 30(1) 109-112
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
Grouping of goats
Group (1)
It included 4 normal post-partum lactating goats Each goat was injected intravenously into
the left jugular vein ceftriaxone These goats were left for 15 days after the intravenous
injection to insure complete excretion of ceftriaxone from bodies of goats Then each goat
was injected intramuscularly into the gluteus medius muscle with the same dose of
ceftriaxone The aim of intramuscular injection to calculate the bioavailability of ceftriaxone
in normal goats
Group (2)
It included 4 normal post-partum lactating goats Each goat was injected intramuscularly into
the gluteus medius muscle with 20 mgkg bwt ceftriaxone for five consecutive days
Group (3)
It included 4 experimentally infected post-partum lactating goats with twenty four hours
peptone water culture of enterpathogen Salmonella typhimurium which were cultured on
nutrient agar plates for 24 hours then suspension of culture were collected by sterile saline
By opacity tube the required concentration of 2Χ109 micro-organismsml was obtained Each
of the four goats received orally a 10 ml suspension containing 2x109
organismml The
clinical symptoms of bacteraemia as fever and diarrhea appeared after 48-72 hours of
injection with Salmonella typhimurium suspension[17]
Each goat was injected
intramuscularly into the gluteus medius muscle with ceftriaxone per kilogram body weight
48 hours after experimental infection with samlonella Typhmurium for five consecutive days
Collection of samples
Blood samples
Blood samples were collected from right jugular vein following a single intravenous injection
of ceftriaxone in normal goats blood samples were collected after 5 min 10 min15 min 30
min 1 2 4 8 and 12 hours of administration Blood samples following the second third
fourth and fifth intramuscular doses were collected before and 10 min 15 min 050 1 2 4 8
and 12 hours post injection Blood samples taken from goats were allowed to clot and the
serum separated by centrifugation collected and divided in to two parts the first part was
used for assay of ceftriaxone and the second part was used for creatinine assay All serum
samples were stored at ndash 20degC until assay for ceftriaxone and creatinine
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Urine samples
The urine sample was taken by using rubber balloon catheter (Folatex No 4158512) The
goats were catheterized and bladder was evacuated before each experiment Following
injection of ceftriaxone (single intravenous single intramuscular and repeated intramuscular
administration) in goats (normal and experimentally infected) urine samples were taken after
025 050 1 2 4 8 12 24 and 48 hours of administrations Urine sample which was taken
at 025 h was discarded Urine samples from goats of group (1) group (2) group (3) were
collected and divided into two parts the first part was used for assay of ceftriaxone and the
second part was used for creatinine assay All urine samples were stored at - 20degC until assay
for ceftriaxone After the end of each experiment the urinary bladder was irrigated with 15
milliliters potassium permanganate solution 1 5000 as antiseptic agent
Milk samples
The udder was completely evacuated before drug administration and milk samples were
collected by hand stripping from both teats Following injection of ceftriaxone (single
intravenous single intramuscular and repeated intramuscular administration) in goats (normal
and experimentally infected) milk samples were taken after 050 1 2 4 8 12 24 and 48
hours of administrations Milk sample which was taken at 025 h was discarded The udder of
each goat in all groups was completely evacuated before drug administration and after each
milk samples Milk samples from goats of all groups were allowed to clot (by mixing equal
volumes of milk and 25 trichloroacetic acid) and centrifuged The skim milk was collected
and stored at ndash 20degC until assay for ceftriaxone
Analytical Procedure
Assay of ceftriaxone
Ceftriaxone was assayed in goats serum distalled water and goats milk by microbiological
method using agar well diffusion method by using of Escherichia coli ATCC (American
type culture collection 25922) as tested microorganism which was obtained from
Microbiological Department Animal Health Institute Doky Giza Egypt)[18]
Concentrations of ceftriaxone in biological fluids were determined by modification of the
agar ndash plate diffusion method[19]
using Escherichia coli ATCC25922 as assay organism and
Muller Hinton agar media
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Assay of samples
According to[20]
three plates were used for each sample Six pores were made three of them
were filled with reference concentration while the other three pores were filled with the
serum milk or urine samples in triplicate manner The plates were incubated at 37degC for 18
hours then the diameter of inhibitory zones were measured The diameter of inhibitory zones
of samples were corrected by using the zone diameter of the reference concentration in the
same manner as previously discussed either by addition or subtraction From the standard
curve the concentrations corresponding to the corrected values of the inhibitory zones were
obtained
Drug clearance
Clearance of the tested drug from the blood of goats was estimated according to the following
equation
Drug clearance10 kg b wt =
Drug concentration in urine (microgml) X rate of diuresis (mlmin) Body weight (Kg)
_________________________________________________________________
Drug concentration in serum (microgml) X 10
Assay of creatinine in serum and urine
Creatinine was assayed by[21]
and performed by kit manufactured by Diamond diagnostics
company
Creatinine clearance
The creatinine clearance (mlmin10 kgbwt) for goats was calculated by the following
equation
Creatinine clearance 10 kgbwt =
Creatinine concentration in urine (mgL) X rate of diuresis (mlmin) Body weight (Kg)
______________________________________________________________________
Creatinine concentration in serum (mgL) X 10
Pharmacokinetic analysis
The pharmacokinetic parameters were calculated by using Winonlin version 12 and other
parameters according to[2223]
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Statistical Analysis
The data were calculated as mean plusmn standard error All statistical analysis were carried out
according to[24]
using the scientific calculator CASIO fx 120
RESULTS
Following a single intravenous injection of 20 mg ceftriaxonekg bwt in normal goats
ceftriaxone could be detected therapeutically for 8 hours post intravenous injection The
serum concentration ndash time curve of ceftriaxone following intravenous injection showed that
the drug obeyed a two compartments open model (Figure 1) The disposition kinetics of
ceftriaxone following a single intravenous intramuscular injection were recorded in table (1)
Intramuscular injection of 20 mg ceftriaxone per kilogram body weight twice daily for five
consecutive days in normal and Salmonella typhimurium infected goats revealed a lower
significant serum ceftriaxone concentration after the first third fifth seventh ninth doses in
Salmonella typhimurium infected goats compared with normal goats The pharmacokinetic
parameters of ceftriaxone after repeated intramuscular injection in normal were compared to
those in Salmonella typhimurium infected goats (Table 2) and (Figure 2 amp 3)
The highest concentrations of ceftriaxone in milk were recorded 4 hours after each
intramuscular dose (Table 3) with a significant lower value in Salmonella typhimurium
infected goats compared with normal goats The calculated milkserum concentrations ratios
of ceftriaxone after repeated intramuscular injection (Table 4)
The amount of urine (mlmin) voided after repeated intramuscular injection of 20 mgkg bwt
Twice daily of ceftriaxone for five consecutive days in normal and experimentally
Salmonella typhimurium infected goats were recorded in table (5) The mean peak urine
concentrations of ceftriaxone (Table 6) were reached 2 hours after each intramuscular dose
with a lower significant concentration in Salmonella typhimurium infected goats compared
with normal goats Urineserum concentration ratios of ceftriaxone after repeated
intramuscular injection in normal and experimentally Salmonella typhimurium infected goats
were calculated and illustrated in table (7) Creatinine clearance (mlmin10 kg bwt)
expressing glomerular filtration rate from blood of goats was shown in table (8) The rate of
ceftriaxone clearance (mlmin10 kg bwt) from blood of goats was shown in table (9) The
ratio between ceftriaxone clearance and creatinine clearance was calculated and illustrated in
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
table (10) The data revealed a significant lower ratio in Salmonella typhimurium infected
goats compared with normal goats after the third fifth seventh ninth doses
Table (1) Pharmacokinetics parameters of ceftriaxone (μgml) following a single
intravenous and intramuscuer injection of 20 mgkg bwt in normal goats (n=4)
Intramusculer_
(XplusmnS E)
Intravenous_
(XplusmnS E) Unit Parameters
-------- 1213 plusmn321321 microgml Cdeg
4360plusmn12343 61390 plusmn330 microgml A
43440plusmn43660 636 plusmn43316 h-1
α
43433plusmn3340 43340 plusmn43442 H (α) 43 T
43420plusmn43233 4333plusmn131 h-1
K12
43446plusmn43400 43409plusmn231 h-1
K21
-------- 43440plusmn431 lkg Vdss
4321plusmn6340 43636plusmn1303 microgml B
434446plusmn43419 43443plusmn43136 h-1
β
43141plusmn39340 43411plusmn331 H t05(β))
4344plusmn43401 434440plusmn43409 lkgh Cl tot
-------- 1136plusmn2111300 microgmlh AUMC
-------- 43303 plusmn0314 H MRT
9300plusmn2439 30plusmn034330 microgmlh AUC
3392plusmn63329 -------- F
43436plusmn4361 -------- h-1
K01
43420plusmn3346 -------- h-1
T05(k01)
4342plusmn330 -------- H Tmax(calc))
43021plusmn04343 -------- μgml Cmax(calc)
Cdeg Drug concentration in the serum at zero time immediately after a single intravenous
injection (μgml) A amp B Zero time plasma drug concentration intercepts of biphasic
intravenous disposition curve The coefficient B is based on the terminal exponential phase
(μgml) α amp β Hybrid rate constant of biphasic intravenous disposition curve values of α
and β are related to the slopes of distribution and elimination phase respectively of
biexponential drug disposition curve (h-1
) T05 (α) Distribution half ndash life (h) t05 (β)
Elimination half ndash life (h) K12 First ndash order transfer rate constant for drug distribution from
Central to peripheral compartment (h-1
) K21 First order transfer rate constant for drug
distribution from Peripheral to central compartment (h-1
) Vdss The apparent volume of
distribution which was calculated by steady ndash state method (mlkg) AUMC Area under
moment curve MRT Mean residence time AUC Total area under the serum drug
concentration versus time curve from t = 0 to t = α after administration of a single dose F
Bioavailability Cmax maximum drug concentration Tmax time of maximum observed
concentration in blood
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
Figure (1) Arthimatic plot of Serum concentrations of ceftriaxone (μgml) in normal
goats following a single intramuscular injection )diamsdiams( previously given the same doseby
a single intravenous injection () of 20 mg ceftriaxonekgbwt (n=4)
Figure (2) Semilogarthmic graph depicting the time course of ceftriaxone in serum of
normal goats following repeated ntramuscular injection of 20 mg ceftriaxonekgbwt
twice dialy for five consecutive days (n=4)
Figure (3) Semilogarthmic graph depicting the time course of ceftriaxone in serum of
experimentally Salmonella typhimurim infected goats following repeated ntramuscular
injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4) 3
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
Table (2) Pharmacokinetic parameters of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected
goats following repeated ntramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)
Dose
Unit
عىهParameters
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1269plusmn0073 7409plusmn121 1352plusmn0132 6373plusmn147 1410plusmn0243 5923plusmn126 1461plusmn0214 5430plusmn125 1424plusmn0172 7635plusmn176 gmlmicro A
0651plusmn0049 plusmn000843116 0720plusmn0008 plusmn00413300 0823plusmn0006 plusmn00263322 0848plusmn0025 plusmn00233323 0786plusmn0028 133plusmn0033 h-1 Α
106plusmn0008 330plusmn0015 0962plusmn0011 0392plusmn0007 0841plusmn0007 0567plusmn012 0818plusmn0024 0569plusmn0012 0885plusmn0030 plusmn00124322 H T05(α)
248plusmn0019 168plusmn0047 203plusmn0075 181plusmn0033 267plusmn0039 120plusmn0028 248plusmn0060 122plusmn0026 222plusmn0100 136plusmn0027 h-1 Kab
0278plusmn0002 0412plusmn0009 0342plusmn0012 0383plusmn0008 0252plusmn0009 0567plusmn0011 0279plusmn0005 00569plusmn0011 0314plusmn0014 0 510plusmn0012 H T05(ab)
0627plusmn0008 0378plusmn0007 0430plusmn0008 0402plusmn0008 0113plusmn00027 0424plusmn0009 0117plusmn0004 0394plusmn0008 0116plusmn0003 0239plusmn0005 h-1 K12
121plusmn0013 0962plusmn0022 141plusmn0021 130plusmn0023 0666plusmn0019 0651plusmn0013 0683plusmn0020 0660plusmn0013 0761plusmn0039 0998plusmn0023 h-1 K21
115plusmn0035 129plusmn0026 104plusmn0047 112plusmn0024 106plusmn0037 122plusmn0025 110plusmn0077 119plusmn0023 0910plusmn0032 123plusmn0023 H Tmax
4182plusmn0628 6108plusmn140 3440plusmn0363 5135plusmn0860 3117plusmn0965 4774plusmn0854 2713plusmn0781 4243plusmn0 870 2479plusmn0547 4065plusmn0825 gmlmicro Cmax
4944plusmn0820 7195plusmn142 4199plusmn0702 6511plusmn130 3190plusmn0688 5117plusmn113 3185plusmn0909 4709plusmn0990 3256plusmn0918 6329plusmn139 gmlmicro B
0164plusmn0003 0189plusmn00043 0181plusmn0002 0178plusmn0004 0181plusmn00035 0167plusmn0004 0214plusmn0009 0195plusmn0005 0249plusmn0918 0272plusmn0006 h-1 β
423plusmn0079 367plusmn0086 381plusmn0047 388plusmn0089 382plusmn0074 415plusmn0081 325plusmn0139 355plusmn0075 277plusmn0056 255plusmn0050 H T05β
0879plusmn0015 0429plusmn0009 109plusmn0004 0426plusmn0009 133plusmn0022 0503plusmn0011 154plusmn0064 0675plusmn0013 171plusmn0060 0693plusmn0014 Lkgh Cltot
28358plusmn215 40775plusmn808 21784plusmn0888 34259plusmn720 17860plusmn155 30705plusmn601 15281plusmn239 24135plusmn555 12175plusmn144 20292plusmn487 gmlhmicro AUC
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (3) Milk concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats
following repeated ntramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)
Dose Time of
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
197plusmn0205 200plusmn0408 125plusmn0104 155plusmn0132 0887plusmn0013 0885plusmn014 0500plusmn0040 074plusmn0012 ------------ ------ Before
200plusmn0408 22plusmn0108 197plusmn0205 200plusmn0408 155plusmn0132 197plusmn0205 100plusmn000 155plusmn0132 ----------- -------- 050
526plusmn0166 700plusmn0408 300plusmn0408 64plusmn0163 25plusmn0204 600plusmn0408 155plusmn0132 582plusmn0118 100plusmn000 520plusmn0166 1
640plusmn0163 900plusmn0408 582plusmn0118 792plusmn0114 582plusmn0118 755plusmn0221 275plusmn0061 700plusmn0408 200plusmn0408 691plusmn0176 2
900plusmn0408 1512plusmn0125 640plusmn0163 1475plusmn0322 640plusmn0163 1400plusmn0408 600plusmn0408 1352plusmn0205 526plusmn166 1225plusmn0595 4
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350plusmn0353 400plusmn0408 300plusmn0408 392plusmn0125 300plusmn0408 35plusmn0353 275plusmn006 300plusmn0408 155plusmn0132 275plusmn0061 6
300 plusmn0408 35plusmn0353 125plusmn0104 200plusmn0408 125plusmn0104 155plusmn01 0825plusmn0062 100plusmn000 0500plusmn0040 0887plusmn0013 8
200plusmn0408 22plusmn0108 100plusmn000 155plusmn0132 100plusmn000 125plusmn0104 0730plusmn002 0825plusmn0078 0422plusmn000 073plusmn0020 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (4) Milkserum concentrations ratios of ceftriaxone in normal and experimentally Salmonella typhimurim infected
goats following repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice daily for five consecutive days (n=4)
Dose Time of
a
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
0400plusmn0049 025plusmn0063 0307plusmn0026 021plusmn0019 0365plusmn00064 016plusmn0026 0232plusmn0016 0205plusmn0002 -------- helliphelliphelliphellip Before
0057plusmn0125 0042plusmn00025 0062plusmn00062 0042plusmn0010 0575plusmn00062 0055plusmn0006 0067plusmn0016 0049plusmn0005 --------- -------- 050
0127plusmn00062 0115plusmn00064 008plusmn0012 0117plusmn0004 0088plusmn00054 0122plusmn0008 008plusmn0017 0126plusmn0028 0039plusmn0005 0122plusmn0004 1
018plusmn0008 0185plusmn0010 021plusmn0004 017plusmn0004 0182plusmn0054 0179plusmn0006 0112plusmn00025 0193plusmn0012 0097plusmn0020 019plusmn0004 2
0357plusmn0020 0425plusmn0005 033plusmn0021 045plusmn0009 0285plusmn0082 0494plusmn0015 0395plusmn0016 0572plusmn001 0415plusmn0017 054plusmn0027 4
018plusmn0015 016plusmn0016 0207plusmn0022 0175plusmn0006 0257plusmn0037 0180plusmn0017 0272plusmn0015 0201plusmn003 0196plusmn0016 0222plusmn0002 6
0212plusmn0033 0212plusmn0020 0200plusmn0044 0122plusmn0024 0152plusmn0011 014plusmn0022 0122plusmn00062 0102plusmn0001 0107plusmn00094 0117plusmn0002 8
0372plusmn0042 025plusmn001 0325plusmn0027 0192plusmn0014 0265plusmn00064 0185plusmn0015 0272plusmn0125 0195plusmn0012 0252plusmn0032 0275plusmn0009 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
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Table (5) The amount of urine (mlmin) voided in normal and experimentally Salmonella typhimurim infected goats following
repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)
Dose Time of a
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
plusmn00372344 126plusmn0034 130plusmn0030 130plusmn0028 118plusmn0066 118plusmn0067 108plusmn0013 108plusmn0008 ----------- -------- Before
0577plusmn0069 43494057plusmn 045plusmn0060 plusmn0064309 0312plusmn002 033plusmn0012 0340plusmn0024 033plusmn0012 0287plusmn0017 0272plusmn0014 050
0712plusmn0019 0692plusmn0014 068plusmn0081 0697plusmn0006 0672plusmn0011 0675plusmn 0009 0635plusmn0032 0655plusmn0010 0719plusmn0031 0697plusmn0015 1
0837plusmn0025 0787plusmn0021 0732plusmn0011 plusmn00054300 0715plusmn0011 0715plusmn002 0722plusmn0019 0702plusmn0018 0737plusmn0027 0762plusmn0041 2
0535plusmn0095 0507plusmn0021 0447plusmn0022 0452plusmn002 0402plusmn0075 0405plusmn0011 0400plusmn0057 0397plusmn0009 0380plusmn0004 038plusmn001 4
0437plusmn00094 0432plusmn0008 0400plusmn0010 0405plusmn0002 0380plusmn0007 plusmn00044319 0372plusmn0047 037plusmn 0007 0350plusmn0005 0365plusmn0006 6
0397plusmn0028 0410plusmn0008 0380plusmn0012 0395plusmn0009 0355plusmn0086 0352plusmn0007 0340plusmn0004 0345plusmn0005 0302plusmn0004 0335plusmn0005 8
0385plusmn001 0380plusmn0010 0385plusmn00064 0380plusmn0008 0365plusmn0064 0367plusmn0004 0362plusmn0086 0372plusmn0106 0327plusmn0006 0362plusmn0016 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (6) Urine concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats
following repeated intramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)
Dose Time of a
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1125plusmn150 1125plusmn15 735plusmn287 81plusmn324 183plusmn03 555plusmn798 37plusmn0811 1815plusmn43290 -------------- ------ Before
2415plusmn357 2625plusmn374 1695plusmn788 249plusmn574 10575plusmn64 2415plusmn357 5400plusmn273 2085plusmn991 102plusmn160 168plusmn547 050
26025plusmn787 2923plusmn479 22425plusmn1225 2805plusmn35 1695plusmn618 2705plusmn471 10200plusmn547 2415plusmn357 6975plusmn225 22425plusmn894 1
29295plusmn765 3012plusmn346 28575plusmn738 2964plusmn415 2355plusmn259 2923plusmn479 1635plusmn561 2645plusmn917 102plusmn547 24825plusmn616 2
23475plusmn430 2482plusmn616 23475plusmn1564 2415plusmn357 1695plusmn788 198plusmn848 8475plusmn309 1515plusmn708 60plusmn212 1185plusmn45 4
1905plusmn45 2355plusmn259 153plusmn519 1935plusmn960 114plusmn948 159plusmn173 6675plusmn309 1215plusmn45 1312plusmn0552 855plusmn193 6
153plusmn1024 1965plusmn135 1335plusmn1229 150plusmn34 735plusmn295 1365plusmn665 6181plusmn339 72plusmn244 907plusmn0951 5025plusmn143 8
135plusmn519 120plusmn346 11725plusmn1551 96plusmn874 525plusmn295 75plusmn173 153plusmn130 39plusmn212 3735plusmn0458 13125plusmn0552 12
Between normal and diseased
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Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (7) Urineserum concentrations ratios of ceftriaxone following repeated ntramuscular injection of 20 mg
ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats
(n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
229plusmn 163 1448plusmn0743 1885plusmn159 1125plusmn0484 533plusmn0260 1050plusmn358 175plusmn0380 4146plusmn116 ------- ------ Before
741plusmn0063 plusmn01553 58plusmn0242 plusmn0149390 422plusmn0206 683plusmn0106 245plusmn0092 667plusmn0306 0510plusmn0081 559plusmn0181 050
651plusmn0243 plusmn0065031 637plusmn0373 plusmn014431 565plusmn0243 plusmn0085300 360plusmn0303 plusmn0110312 279plusmn0121 534plusmn0248 1
836plusmn0150 plusmn00476322 862plusmn0180 plusmn010463 942plusmn0166 plusmn0130631 217plusmn0303 727plusmn0256 508plusmn0186 plusmn01680340 2
939plusmn0235 plusmn01580344 1006plusmn0710 plusmn00750310 999plusmn0542 plusmn02850344 565plusmn0223 641plusmn0241 48plusmn0164 plusmn014834 4
1005plusmn0418 2plusmn018813 1097plusmn0641 plusmn03979300 993plusmn0921 plusmn0252931 619plusmn0483 plusmn0362933 167plusmn0101 642plusmn0644 6
1091plusmn0649 plusmn075332339 1171plusmn0980 995plusmn0415 925plusmn0593 plusmn05593433 886plusmn0408 plusmn02510311 2055plusmn0311 plusmn02046310 8
2392plusmn129 plusmn032731396 1794plusmn0228 1222plusmn124 1418plusmn109 plusmn026733336 580plusmn0397 plusmn03951326 227plusmn0452 plusmn02740316 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (8) Creatinine clearance (mlmin10kgbwt) following repeated intramuscular injection of 20 mg ceftriaxonekgbwt
twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats (n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1115plusmn0703 2265plusmn167 481plusmn0409 672plusmn0817 669plusmn0672 1202plusmn0777 695plusmn0634 1724plusmn179 ----------- ------ Before
0703plusmn0091 147plusmn0305 0718plusmn0141 251plusmn0707 0547plusmn0055 0699plusmn0092 0802plusmn0099 103plusmn0106 295plusmn0124 0458plusmn0037 050
101plusmn0075 161plusmn0093 131plusmn0099 264plusmn0217 161plusmn0146 373plusmn0499 247plusmn0110 4755plusmn0582 214plusmn0234 103plusmn0166 1
157plusmn0198 387plusmn0340 173plusmn0501 267plusmn0217 187plusmn0563 287plusmn0499 451plusmn0223 972plusmn105 263plusmn0399 169plusmn0454 2
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
184plusmn0095 346plusmn0444 173plusmn0501 436plusmn0599 383plusmn0299 682plusmn0584 328plusmn0253 119plusmn153 123plusmn0057 292plusmn0742 4
221plusmn0242 411plusmn0661 241plusmn0186 663plusmn0584 308plusmn0234 422plusmn0314 353plusmn0393 548plusmn0901 105plusmn0057 264plusmn0294 6
261plusmn0295 476plusmn0339 319plusmn0273 753plusmn0676 106plusmn0207 0773plusmn0049 228plusmn0175 456plusmn0340 206plusmn0160 404plusmn0419 8
310plusmn0218 409plusmn0434 3264plusmn0153 669plusmn0476 209plusmn0189 235plusmn0337 217plusmn0143 377plusmn0342 240plusmn0218 6055plusmn0176 12
Between normal and diseased
Plt 005 Plt001 Plt0001
Table (9) Ceftriaxone clearance (mlmin10kgbwt following repeated intramuscular injection of 20 mg ceftriaxone kgbwt
twice in normal and experimentally Salmonella typhimurim infected goats (n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1048plusmn121 0557plusmn684 895plusmn113 0547plusmn560 238plusmn0222 103plusmn 480 0668plusmn0157 0173plusmn216 -------- ----------- Before
156plusmn0251 43204plusmn3322 0936plusmn0162 43211plusmn3334 0473plusmn0037 43469plusmn43964 0300plusmn0028 43341plusmn080 0190plusmn0137 43400plusmn43642 050
166plusmn0079 43323plusmn3311 157plusmn0178 43419plusmn3301 137plusmn0115 43311plusmn33022 0883plusmn0054 43341plusmn 133 0616plusmn0153 43120plusmn3301 1
254plusmn0272 43361plusmn3391 222plusmn0093 4331plusmn3390 243plusmn0180 43209plusmn3309 183plusmn0149 43310plusmn2340 128plusmn0153 43312plusmn3390 2
181plusmn0136 43339plusmn3316 161plusmn0129 433plusmn3329 144plusmn0100 43412plusmn3349 0821plusmn0072 0063plusmn0977 0654plusmn0065 43400plusmn4306 4
160plusmn0177 43393plusmn336 152plusmn0200 43416plusmn331 135plusmn0118 4332plusmn3322 0897plusmn0052 43304plusmn3330 0212plusmn0022 43460plusmn43112 6
153plusmn0049 43291plusmn234 163plusmn0242 43346plusmn3300 0891plusmn0272 43306plusmn3310 108plusmn0071 43416plusmn04310 0229plusmn0046 43490plusmn43916 8
340plusmn0522 43214plusmn2341 249plusmn0150 43112plusmn3393 186plusmn0159 43320plusmn336 0773plusmn0094 43390plusmn 134 0264plusmn0043 43400plusmn 54369 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
Table (10) Ceftriaxone clearancecreatinine clearance following repeated ntramuscular injection of 20 mg
ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats
(n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
0934plusmn0083 0305plusmn0013 183plusmn0116 0864plusmn0098 0358plusmn0018 0279plusmn0047 0099plusmn0020 0127plusmn0001 ------- ----------- Before
220plusmn0115 0819plusmn0044 131plusmn00414 0458plusmn0029 0876plusmn0063 126plusmn0068 0361plusmn0011 0813plusmn0031 0018plusmn0003 108plusmn0062 050
164plusmn0078 0818plusmn0029 118plusmn0068 0546plusmn0027 0858plusmn0052 0407plusmn0041 0331plusmn0009 0287plusmn0025 0324plusmn0011 0909plusmn0187 1
161plusmn0044 0488plusmn0005 232plusmn128 0329plusmn0027 169plusmn0464 0686plusmn0050 0409plusmn0020 0220plusmn0029 0512plusmn0077 266plusmn177 2
0933plusmn0024 0394plusmn0005 0948plusmn0062 0296plusmn0007 0381plusmn0027 0160plusmn0008 0235plusmn0014 0083plusmn0006 0528plusmn0028 0362plusmn0041 4
0726plusmn0018 0411plusmn0028 0639plusmn0066 0204plusmn0006 0446plusmn0034 0286plusmn0008 0238plusmn0019 0214plusmn0006 020plusmn0013 0382plusmn0028 6
0609plusmn0072 0425plusmn0036 0508plusmn0052 0192plusmn0009 0524plusmn0146 174plusmn0083 0477plusmn0015 0213plusmn00018 0109plusmn0185 0222plusmn0006 8
108plusmn0128 0496plusmn0012 0942plusmn0004 0265plusmn0030 0891plusmn0056 0706plusmn0103 0351plusmn0022 0354plusmn0018 0111plusmn0021 0098plusmn0018 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
DISCUSSION
In the present investigation intravenous injection of 20 mg ceftriaxonekgbwt in normal goats the drug showed high serum level
(92plusmn 0408 μgml) at 5 minutes post-injection then its concentration was decreased gradually till reached its minimum level (18
plusmn0816μgml) at 8hours post-injection
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In the present investigation the intravenous injection of 20 mg ceftriaxonekgbwt In normal
goats showed that the drug disposition best fitted a two-compartments- open model a
compartment of plasma and rapid equilibrating tissues and a deeper slower compartment
The obtained result is consistent with those reported for ceftriaxone in lactating goats[9]
lactating ewe[25]
domestic cat[15]
calves[26]
and patanwadi sheep[8]
Also this phenomenon is
in agreement with those reported for other cephalosporines as ceftazidime in a rabbit[27]
cefepime in dog and neonatal foals[28]
ewes[29]
ceftriaxone in goats[9]
cefipime in calves[30]
ceftiofur in cross-bred friesian cattle[31]
cefipime in calves[32]
ceftiofur in cows[33]
cefpirome
in cross-bred calves[3]
cefazidime in goats[35]
and cefquinome in sheep and goats[36]
cefipime
in chickens[37]
Ceftriaxone was distributed after intravenous injection with a distribution phase (α) equal to
656 per hour with a short distribution half ndash life [t05 (α)] equal to 0104 hour The shorter
distribution half-life of ceftriaxone in goats suggested the rapid distribution of the drug in
body tissue and fluid and that nearly similar to that recorded for ceftriaxone in lactating
goats(012 hour)[9]
for ceftriaxone in lactating ewes (0152 hour)[2]
and for ceftriaxone in
calves( 013hour)[26]
The rapid distribution of ceftriaxone in goats is supported by high rate constant of transfer of
the drug from central to peripheral compartment [K12 = 353 h-1
] as compared to the rate
constant of transfer of the drug from peripheral to central compartment [K21= 295 h-1
] This
value is nearly similar to those reported for cefotaxime in goats (K21=327 h-1
)[38]
On contrast
this value was higher than those recorded for ceftriaxone in lactating goats (K21=143 h-1
)[9]
in
lactating ewes (K21=125 h-1
)[25]
and in domestic cats (K21=154 h-1
)[15]
The apparent volume of distribution of ceftriaxone was (0355plusmn0004LKg) this value is
nearly similar to that recorded for cefaronide in sheep(039 LKg)[7]
cefotaxime in dog (048
lkg)[39]
in goat (051 lkg)
[40] for caphalexin in buffalo calves (041 Lkg)
[41] for cefipime in
ewes and calves (032 lkg) (043Lkg)[29]
and[30]
respectively For ceftriaxone in domestic
cats (057Lkg)[15]
in camel (032Lkg)[42]
On the other hand this result is differ than that
reported for cefotaxime in buffalo calves (117Lkg)[43]
High value of the volume of
distribution suggested extensive penetration power Drug with volume of distribution greater
than one literkilogram indicated wide distribution or extensive tissue binding or both[44]
The
apparent volume of distribution in the present study indicated moderate tissue penetrating
power This result agreed with[15]
for ceftriaxone in domestic cats
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Ceftriaxone is eliminated in the current study following a single intravenous injection with
elimination half ndashlife [t 05(β)] equal to 519 hours This observation is nearly agreed with the
data recorded for ceftizoxime in goats (624hours)[45]
On contrast this value was longer than
that reported for ceftriaxone in lactating ewe (175hours)[25]
for cefaronide in sheep (17
hours)[7]
For cephalexin in buffulo calves (216hours)[41]
for ceftriaxone in healthy horse
(162hours)[46]
also this value is longer than that recorded for ceftriaxone in lactating goats
(144hours)[9]
for cefipime in goats (186hours)[47]
The rate of total body clearance of ceftriaxone following a single intravenous injection is
0048 lkgh which equal to data reported for ceftizoxime in lactating goats (005Lkgh)[45]
On contrast this value is lower than that reported for ceftriaxone in buffulo calves lactating
goats buffulo calves (Bubalus bubalis) goats (capra hircus) patanwadi sheep (026 Lkgh)
(395 Lkgh) (440 Lkgh) (450 Lkgh) (391 Lkgh)[12913118]
respectively
The variation in total body clearance might be attributed to specific interspecies variation
handling of the drug method used healthy status of the animal[48]
The difference between values calculated for pharmacokinetic parameters may be attributed
to animal species the drug formulation employed the age the size or sex o l lf the animal
or even inter individual variation and also due to method of analysis of the drug[49]
Following a single intramuscular injection of 20 mg ceftriaxonekg bwt In normal goats the
drug reached its peak serum concentrations after one hour of injection with value
of(41μgml) Ceftriaxone could be detected in serum in a therapeutic level (263μgml) at 12
hours post-injection The reported peak serum concentrations neerly similar to that reported
for cephalexin in buffulo calves (457 microgml)[41]
These results is differed than those reported
for ceftriaxone in cross breed calves (188 microgml at 30 min[16]
in Kangro breed of goats
(Capra Hircus) (2640 microgml at 20 min[10][50]
found after intramuscular administration of
ceforazone peak plasma concentration was (976 microgml) at 45min This result was also higher
than that recorded for ceftriaxone in buffalo calves (158 microgml)[13]
The calculated maximum serum concentration (Cmax) is (40015 microgml) at maximum time
(tmax) of 157 hours The reported (Cmax) agreed with the data reported for cefipime in goats
(4932 microgml[47]
The reported maximum serum concentration (Cmax) is higher than that
reported for ceftriaxone in lactating goats(236 microgml)[9]
in lactating ewes (1722 microgml[25]
in
wwwwjppscom Vol 5 Issue 01 2016
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
goats (2151 microgml)[11]
for cefquinome in camels (123 microgml)[51]
for ceftriaxone in calves
(1534 microgml)[26]
in patanwadi sheep (1553 microgml)[8]
for cefpirome in cattle (101 microgml)[52]
And for ceftiofur in chickens (2594 μgml)[37]
On the other hand the result was lower than
that reported by[6]
who observed the maximum serum concentration (Cmax) of ceftriaxone in
human after ntramuscular administration was (805 microgml) also it was lower than that
reported for ceftriaxone in dog (11510 microgml)[53]
in domestic cats (5440 microgml)[15]
and for
ceftazoxime in goats (8878 microgml)[45]
The reported [tmax] is neerly similar to that reported for ceftriaxone (104hours)in lactating
ewes by[25]
On contrast it is longer than those reported for ceftriaxone in dogs
(129hours)[53]
for ceftriaxone in lactating goats (07hours)[9]
also the result was longer than
that reported for ceftriaxone in domestic cats (033hours)[15]
in buffulo calves (05 hours)[13]
and for cefpirome in cattle (075hours)[52]
The reported [tmax] is shorter than those reported
for cefquinome in camels (425hours)[51]
in sheep and goats (261 and 262 hours)[36]
and for
ceftiofur in chickens (251 hours)[37]
The elimination half life [t05(β)]
following a single intramuscular administration was 1804 hours This value is nearly agreed
with that recorded for cefquinomein camels (1024hours)[52]
On contrast this result is longer
than that reported for cephalexin in buffalo calves (243hours)[41]
for ceftriaxone in lactating
ewes (177hours)[25]
in buffalo calves (438hours)[13]
in goats (203 hours)[11]
and for
cefipime in goats (165 hours)[47]
The rate of total body clearance of ceftriaxone following a single intramuscular injection is
0043lkgh This value was lower than that reported for ceftriaxone in buffulo calves
(401Lkgh)[13]
in goats (304 Lkgh)[11]
and in sheep (222 Lkgh)[8]
Bioavailability is the fraction of the drug administered by non vascular rout that gains
accesses to the systemic circulation The obtained result revealed that the calculated systemic
bioavailability percent was 6128 It is equal to that recorded for cefpirome in cow calves
(61)[54]
It is nearly equal to that recorded for ceftriaxone in sheep (64)[8]
On the other
hand this value is higher than those recorded for cefperazone in crossbred calves (481)[50]
for ceftriaxone in goats (59)[11]
in calves (47)[55]
On contrast this value is lower than
those reported for cefotaxime in two cats 982 and 93)[57]
for cephradine in goats
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
(739)[58]
for ceftazidime in a rabbit (966)[27]
for ceftriaxone in lactating goats (85)[9]
in lactating ewes (836)[25]
in domestic cats 8572[15]
for cefipime in goats 8645[47]
for ceftriaxone in buffulo calves 702[13]
and for ceftiofur in chickens 8890[37]
Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium
infected goats twics dialy for five days revealed that the drug could be detected in a
therapeutic level for 12hours following repeated intramuscular administrations and exceeded
the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]
The relative higher serum concentrations of ceftriaxone after the last dose compared to the
first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12
hours intervals for five consecutive days These observations agreed with data reported by[36]
on comparing the data of serum levels of repeated intramuscular injections with first
intramuscular injection it was revealed that repeated intramuscular injections of cefquinome
have cumulative effect in both species sheep and goats
The obtained result is inconsistent with that reported by[56]
who found thatwhen cefotaxime
was administered repetitively in patients the ratio of maximal serum levels after the last dose
to those after the first dose demonstrated minimal accumulation of intact drug and by[60]
who
found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in
buffalo calves
The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium
infected goats are significantly lower than those in normal goats following repeated
intramuscular injection These lower blood concentrations in Salmonella typhimurium
infected goats might be attributed to the higher penetrating power of ceftriaxone to the
diseased tissues[48]
This phenomenon is similar to data recorded by[61]
who suggested that
Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of
ceftriaxone These alterations might be due to fever and inflammation induced by
infections[59]
proved that the serum concentrations of cephradine following intramuscular
administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after
each intramuscular dose with a lower significant values recorded in Escherichia-coli infected
goats than in normal goatsAlso similer to that reported by[62]
who observed that the
maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
in comparison to normal sheepOn contrast[43]
reported that peak plasma level of cefotaxime
in febrile buffalo calves was higher than healthy buffalo calves
In this study the total body clearance (CLtot) in normal goats are significantly lower than in
Salmonella typhimurium infected goats This result supported by[61]
and[63]
fever and
inflammation are cardinal features in bacterial infection which may in turn caused an
increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all
these could lead to increased in the rate at which the drug was delivered to both organs which
were important sites of drug excretion This might somewhat explain the increase in the total
body clearance in infected goats This result is differ than that reported by[64]
who observed
that the clearance of ceftriaxone was significantly reduced in infected mice than in non
infected animals
The highest concentrations of ceftriaxone in milk are recorded 4 hours after each
intramuscular injection with a significant lower value in Salmonella typhimurium infected
goats than in normal goats This might be attributed to accumulation of drug in the inflammed
tissues[48]
This result is similar to those reported by[6559]
who found that milk concentrations
of gentamicin and cephradine were significantly lower in infected goats and cattle than in
normal ones respectively
The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the
non-ionic passive diffusion principle[66]
reported that most drug cross-lipid membranes by
passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly
influenced by the physicochemical properties of the drug[6768]
Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum
ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the
physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]
Milk
contains substantially more lipid and less protein than serum and is slightly more acidic
Therefore drugs which tend to concentrated in milk are weak bases with low serum protein
binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide
and aminothiazole also possesses an hydroxytriazinone group as new and additional
ionization center[70]
these compounds are sufficiently lipid- soluble to be able to penetrate
tissues
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
The dose of ceftriaxone used in the present study induced therapeutically concentrations in
milk These concentrations suggested that ceftriaxone would be efficacious in treatment of
mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily
for 3-5 days
The study showed that the urine concentrations of ceftriaxone are greater than the concurrent
serum concentrations following intramuscular injection This observation is similar to those
reported in cows after cephapirin administrations[71]
In the present study urine concentrations of ceftriaxone increased with the repetition of
dosing This observation supported by[72]
after repeated intramuscular administrations of
ceftriaxone in healthy volunteeres
The mean peak urine concentrations of ceftriaxone were reached 2 hours after each
intramuscular injection The lower urine ceftriaxone concentrations in Salmonella
typhimurium infected goats than in normal goats might be attributed to the accumulation of
the drug in the inflamed tissues[48]
The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower
ratio in Salmonella typhimurium infected goats than in normal goats at different time of
sampling This indicates that glomerular filteration seemed to be the main pathway of
ceftriaxone elimination This observation supported by[59]
who found that the ratio between
cephradine clearance from blood of goats to creatinine clearance showed a marked decrease
in Escherichia-coli infected goats than in normal goats This indicated that glomerular
filteration seemed to be the main pathway of cephradine elimination with a limited rate of
tubular reabsorption
CONCLUSION
The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value
referred a better absorption of ceftriaxone from its site of intramuscular administration The
high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular
administrations suggested that ceftriaxone could be used for treatment of mastitis caused by
Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats
The high concentrations of ceftriaxone in urine after repeated intramuscular administrations
suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in
goats
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24 Snedecor GW and Cokran WG (1980) Statistical method 7th
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25 Goudah A Shin HC Shim JH Abd El-Aty AM (2006) Characterization of the
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Vet Pharmacol Ther Aug 29(4) 307-12
26 Jayesh J M Harshad V G Shailesh K B Urvesh D P and Aswin M T (2010)
Pharmacokinetics of ceftriaxone in calves Veterinarski arshiv 80(1) 1-9
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27 Abd-El-Aty AM Goudah A and Abo E S K (2001) Pharmacokinetics
intramuscular bioavailability and tissue residue profiles of ceftazidime in a rabbit
model Dtsch Tierarztl Wochenschr 108(4) 168-171
28 Gardner S Y and Papich M G (2001) Comparison of cefepime pharmacokinetics in
neonatal foals and adult dogs J Vet Pharmacol Therap 24(3) 187-192
29 Ismail M (2005a) Pharmacokinetics of cefepime administered by iv and im routes to
ewes J Vet Pharmacol Therap 28(6) 499-503
30 Patel U D Bhavsar S K and Thaker A M (2006) Pharmacokinetics and dosage
regimen of cefepime following single dose intravenous administration in calves Iran J
Pharmacol Therapeut 5(2) 127-130
31 El-Gendy AAM Tohamy MA and Ismail M (2007) Comparative pharmacokinetic
and renal clearance study of ceftiofur in cross breed friesian and buffalo calves BS Vet
Med J 17(1) 69-77
32 Joshi B and Kumar Sharma S (2009) The pharmacokinetics of cefepime in E coli
lipopolysaccharide induced febrile buffalo calves Veterinarski arhiv 79(6) 523-530
33 Tohamy MA (2008) Pharmacokinetics of ceftiofur sodium administered concomitantly
with dipyrone in healthy and feverish cows J Egypt Soc Pharmacol Exp Ther 29(2)
10-15
34 Rajput N Kumar V D and Sandhu HS (2011) Pharmacokinetics and dosage
regimen of cefpirome in febrile cross-bred calves Iran J Pharmacol Ther 10(1) 17-20
35 Abo-El- Sooud K and Tohamy MA (2011) Comparative pharmacokinetics and milk
concentrations of ceftazidime in healthy and mastitic goats Insight Pharmaceut Sci
1(1) 11-17
36 El-Hewaity M Abd El Latif A Soliman A and Aboubakr M (2014) Comparative
pharmacokinetics of cefquinome (Cobactan 25) following repeated intramuscular
administrations in sheep and goats J Vet Med Doi 949642 1-5
37 El-Sayed M G A El-Komy A A A El barawy A M and Ibrahim D M A (2015)
Pharmacokinetics and tissue residues of ceftiofur in normal and Escherichia coli infected
chickens J Phys Pharm Adv 5(3) 574-582
38 Datta B Mandal TK and Chakraborty A K (2003) Pharmacokinetics of cefotaxime
in goats with experimentally induced kidney damage Ind J pharmacol (35) 173-176
39 Guerrini HV English BP Filippich J L Schneider J and Bourne D W (1986)
The pharmacokinetics of cefotaxime in dog Vet Rec 119(4) 81-83
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40 Atef M Ramadan A Afifi N A and Youssef S A (1990) pharmacokinetic profile
of cefotaxime in goat Res Vet Sci 49(1) 34-38
41 Satish K G Chaudhary RK Srivastiva AK and Garg BD (1990) Pharmacokintics
and dosage regemine of cephalexine in buffulo calves (Bubalis Bubalis following single
intravenous and intramusculer adminsteration Veterinary research commuincation 14
59-62
42 Goudah A (2008) Pharmacokinetic parameters of ceftriaxone after single intravenous
and intramuscular administration in camels (Camelus Dromedarius) Res Vet Sci Jun
84(3) 483-9
43 Sharma SK Srivastava AK and Deore DM (2006) Effect of Ecoli
lipopolysaccharides ndashinduced fever on disposition pattern of cefotaxime in buffalo calves
Veterinarski Arhiv 76(6) 537-545
44 Baggot JD (1977) Priniciple of pharmacokinetics In principle of drug disposition in
domestic animals The physiological Basis of veterinary Clinical Pharmacology 1st ed
WB Saunders Co Philadelphi PA 168-179
45 Karmaker UK Datta BK Patra PH Prashant M Suman S Sar TK Chakaborty
AK and mandal KT (2011) Disposition kinetics of ceftizoxime in healthy and mastitic
goats after intravenous adminsteration Pharmacologyonline 3 935-946
46 Ringger NC Pearson EG Gronwall R Kohlepp S J (1996) Pharmacokinetics of
ceftriaxone in healthy horses Equine Vet J Nov 28(6) 476-9
47 Prawez S Raina R Dimitrova D panka NK Ahanger AA Verma PK (2010) The
pharmacokinetics of cefipime in goats following single dose iv and im adminsteration
Turk j vet Anima Sci 34(5) 427-431
48 Baggot JD (1980) Distribution of antimicrobial agents in normal and diseased animals
JAVMA 19(76) 1085-1090
49 Haddad N S Pedersoli W M Ravis W R Fazeli M H and Carson Jr R L (1985)
Pharmacokinetics of gentamicin at steady-state in ponies serum urine and endometrial
concentrations Am J Vet Res 46(6) 1268-1271
50 Gupta JK Chaudhary RK and Dumka VK (2008) Pharmacokinetics after single
intramuscuker adminsrerarion and in-vitro binding plasma protein of cefoprazone in cross
bred calves Veterinaski Arhiv 78(5) 441-448
51 Al Taher AY (2010) Pharmacokinetics of cefquinome in camels J An Vet Ad 9(4)
848-852
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52 Rajput N Dumka V K and Sandhu HS (2012) Pharmacokinetics and in- vitro
plasma protein binding of cefpirome in cattle Veterinaski Arhiv 82(1) 1-9
53 RebueltoM Albarellos G Ambros L Kreil V Montoya L Bonafine R Otero P
Hallu R (2002) Pharmacokinetics of ceftriaxone administered by the intravenous
intramuscular or subcutaneous routes to dogs J Vet Pharmacol Ther Feb 25(1) 73-6
54 Patel RB Bhavsar SK Solanki PF Patel JH Varia RD Modi Falguni D and
Patel MD (2013) Pharmacokinetics of cefpirome following intravenous and
intramuscular administration in cow calves Sci Int 1(11) 371-374
55 Maradiya J J Goriya H V Bhavsar S K Patel U D and Thaker A M (2010)
Pharmacokinetics of ceftriaxone in calves Veterinarski arhiv 80(1) 1-9
56 Inges R MJ Fillastre J Godin M Leroy A and Humbert G (1982) The
Pharmacokinetics of cefotaxime and its metabolites in subjects with normal and impaired
renal function Clin Infect Dis (4) 379-391
57 Mcelroy D Ravis W R and Clark C H (1986) Pharmacokinetics of cefotaxime in
the domestic cats Am J Vet Res 47(1) 86-88
58 El-Sayed MG Atef M and El-Komy AA (1994) Disposition kinetic of cephradine in
normal and Escherichia coli infected goats Dtsch Tierarztl Wochenschr 101(2) 56-60
59 Soback S and Ziv G (1988) Pharmacokinetics and bioavailability of ceftriaxone
administered intravenously and intramuscularly to calves Am J Vet Res 49 535-538
60 Sharma S K and Srivastava A K (2003) Cefotaxime pharmacokinetics in male
buffalo calves following multiple dosing Veterinarski arhiv 73(4) 191-197
61 Abdulgafar O J Shaibu O B and Emmanuel U E (2011) Effect of Salmonella
typhymurium infection on the pharmacokinetics of ceftriaxone in sokoto red goats Niger
J Basic Applied Sci 19(1) 49-54
62 Ranjan R Birendra K R Amita R and Sanjeet K S (2011) Effect of Effect of E coli E
coli endotoxin induced fever on the pharmacokinetic profile and dosage regimen of
ceftriaxone in sheep (Ovis aries) Veterinarski arhiv 81(4) 423-432
63 Etuk EU and Onyeyili PA (2006) The effect of Salmonella infection on the plasma
kinetic of chloramphenicol in the sokoto red goats Inter J Pharmacol 2(1) 28-32
64 Wang E Bergeron Y and Bergeron MG (2005) Ceftriaxone pharmacokinetics in
interleukin-10-treated murine pneumococcal pneumonia J Antimicrob Chemother 55
721ndash726
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
65 El-Sayed MG Hatem ME and El-Komy AA (1989) Disposition kinetic of
gentamicin in normal and endometric cow using microbiological assay Dtsch Tierarztl
Wochenschr 96(8) 412-415
66 Aramyona JJ Mora J Fraile LJ Garcia MA Abadia AR and Breganate MA
(1996) Penetration of enrofloxacin and ciprofloxacin into breast milk and
pharmacokinetics of the drugs in lacating rabbits and neonatal offspring Am J Vet Res
57(4) 547-553
67 Rusmussen F (1966) Studies on the mammary excretion and absorbtion of drugs Vet
Rec (87) 14-18
68 Alkinson A and Begg E (1990) Prediction of drug distribution into human milk from
physicochemical characteristics Clin Pharmacokinet 18(2) 151-167
69 Kenneth F (1997) Drug distribution in human milk Aust Prescr 20(2) 35-40
70 Aleksić M Savić V Popović G Burić N and Kapetanović V (2005) Acidity
constants of cefetamet cefotaxime and ceftriaxone the effect of the substituent at C3
position J Pharm Biomed Anal 39(3-4) 752-756
71 Prades M Brown M P Gronwall R and Miles N S (1988) Pharmacokinetics of
sodium cephapirin in lactating dairy cows Am J Vet Res 49(11) 1888-1890
72 Holazo A A Patel I H Weinfeld R E Konikoff J J and Parsonnet M (1986)
Ceftriaxone pharmacokinetics following multiple intramuscular dosing Euro J Clin
Pharmacol 30(1) 109-112
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1436
Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
Urine samples
The urine sample was taken by using rubber balloon catheter (Folatex No 4158512) The
goats were catheterized and bladder was evacuated before each experiment Following
injection of ceftriaxone (single intravenous single intramuscular and repeated intramuscular
administration) in goats (normal and experimentally infected) urine samples were taken after
025 050 1 2 4 8 12 24 and 48 hours of administrations Urine sample which was taken
at 025 h was discarded Urine samples from goats of group (1) group (2) group (3) were
collected and divided into two parts the first part was used for assay of ceftriaxone and the
second part was used for creatinine assay All urine samples were stored at - 20degC until assay
for ceftriaxone After the end of each experiment the urinary bladder was irrigated with 15
milliliters potassium permanganate solution 1 5000 as antiseptic agent
Milk samples
The udder was completely evacuated before drug administration and milk samples were
collected by hand stripping from both teats Following injection of ceftriaxone (single
intravenous single intramuscular and repeated intramuscular administration) in goats (normal
and experimentally infected) milk samples were taken after 050 1 2 4 8 12 24 and 48
hours of administrations Milk sample which was taken at 025 h was discarded The udder of
each goat in all groups was completely evacuated before drug administration and after each
milk samples Milk samples from goats of all groups were allowed to clot (by mixing equal
volumes of milk and 25 trichloroacetic acid) and centrifuged The skim milk was collected
and stored at ndash 20degC until assay for ceftriaxone
Analytical Procedure
Assay of ceftriaxone
Ceftriaxone was assayed in goats serum distalled water and goats milk by microbiological
method using agar well diffusion method by using of Escherichia coli ATCC (American
type culture collection 25922) as tested microorganism which was obtained from
Microbiological Department Animal Health Institute Doky Giza Egypt)[18]
Concentrations of ceftriaxone in biological fluids were determined by modification of the
agar ndash plate diffusion method[19]
using Escherichia coli ATCC25922 as assay organism and
Muller Hinton agar media
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
Assay of samples
According to[20]
three plates were used for each sample Six pores were made three of them
were filled with reference concentration while the other three pores were filled with the
serum milk or urine samples in triplicate manner The plates were incubated at 37degC for 18
hours then the diameter of inhibitory zones were measured The diameter of inhibitory zones
of samples were corrected by using the zone diameter of the reference concentration in the
same manner as previously discussed either by addition or subtraction From the standard
curve the concentrations corresponding to the corrected values of the inhibitory zones were
obtained
Drug clearance
Clearance of the tested drug from the blood of goats was estimated according to the following
equation
Drug clearance10 kg b wt =
Drug concentration in urine (microgml) X rate of diuresis (mlmin) Body weight (Kg)
_________________________________________________________________
Drug concentration in serum (microgml) X 10
Assay of creatinine in serum and urine
Creatinine was assayed by[21]
and performed by kit manufactured by Diamond diagnostics
company
Creatinine clearance
The creatinine clearance (mlmin10 kgbwt) for goats was calculated by the following
equation
Creatinine clearance 10 kgbwt =
Creatinine concentration in urine (mgL) X rate of diuresis (mlmin) Body weight (Kg)
______________________________________________________________________
Creatinine concentration in serum (mgL) X 10
Pharmacokinetic analysis
The pharmacokinetic parameters were calculated by using Winonlin version 12 and other
parameters according to[2223]
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
Statistical Analysis
The data were calculated as mean plusmn standard error All statistical analysis were carried out
according to[24]
using the scientific calculator CASIO fx 120
RESULTS
Following a single intravenous injection of 20 mg ceftriaxonekg bwt in normal goats
ceftriaxone could be detected therapeutically for 8 hours post intravenous injection The
serum concentration ndash time curve of ceftriaxone following intravenous injection showed that
the drug obeyed a two compartments open model (Figure 1) The disposition kinetics of
ceftriaxone following a single intravenous intramuscular injection were recorded in table (1)
Intramuscular injection of 20 mg ceftriaxone per kilogram body weight twice daily for five
consecutive days in normal and Salmonella typhimurium infected goats revealed a lower
significant serum ceftriaxone concentration after the first third fifth seventh ninth doses in
Salmonella typhimurium infected goats compared with normal goats The pharmacokinetic
parameters of ceftriaxone after repeated intramuscular injection in normal were compared to
those in Salmonella typhimurium infected goats (Table 2) and (Figure 2 amp 3)
The highest concentrations of ceftriaxone in milk were recorded 4 hours after each
intramuscular dose (Table 3) with a significant lower value in Salmonella typhimurium
infected goats compared with normal goats The calculated milkserum concentrations ratios
of ceftriaxone after repeated intramuscular injection (Table 4)
The amount of urine (mlmin) voided after repeated intramuscular injection of 20 mgkg bwt
Twice daily of ceftriaxone for five consecutive days in normal and experimentally
Salmonella typhimurium infected goats were recorded in table (5) The mean peak urine
concentrations of ceftriaxone (Table 6) were reached 2 hours after each intramuscular dose
with a lower significant concentration in Salmonella typhimurium infected goats compared
with normal goats Urineserum concentration ratios of ceftriaxone after repeated
intramuscular injection in normal and experimentally Salmonella typhimurium infected goats
were calculated and illustrated in table (7) Creatinine clearance (mlmin10 kg bwt)
expressing glomerular filtration rate from blood of goats was shown in table (8) The rate of
ceftriaxone clearance (mlmin10 kg bwt) from blood of goats was shown in table (9) The
ratio between ceftriaxone clearance and creatinine clearance was calculated and illustrated in
wwwwjppscom Vol 5 Issue 02 2016
1439
Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
table (10) The data revealed a significant lower ratio in Salmonella typhimurium infected
goats compared with normal goats after the third fifth seventh ninth doses
Table (1) Pharmacokinetics parameters of ceftriaxone (μgml) following a single
intravenous and intramuscuer injection of 20 mgkg bwt in normal goats (n=4)
Intramusculer_
(XplusmnS E)
Intravenous_
(XplusmnS E) Unit Parameters
-------- 1213 plusmn321321 microgml Cdeg
4360plusmn12343 61390 plusmn330 microgml A
43440plusmn43660 636 plusmn43316 h-1
α
43433plusmn3340 43340 plusmn43442 H (α) 43 T
43420plusmn43233 4333plusmn131 h-1
K12
43446plusmn43400 43409plusmn231 h-1
K21
-------- 43440plusmn431 lkg Vdss
4321plusmn6340 43636plusmn1303 microgml B
434446plusmn43419 43443plusmn43136 h-1
β
43141plusmn39340 43411plusmn331 H t05(β))
4344plusmn43401 434440plusmn43409 lkgh Cl tot
-------- 1136plusmn2111300 microgmlh AUMC
-------- 43303 plusmn0314 H MRT
9300plusmn2439 30plusmn034330 microgmlh AUC
3392plusmn63329 -------- F
43436plusmn4361 -------- h-1
K01
43420plusmn3346 -------- h-1
T05(k01)
4342plusmn330 -------- H Tmax(calc))
43021plusmn04343 -------- μgml Cmax(calc)
Cdeg Drug concentration in the serum at zero time immediately after a single intravenous
injection (μgml) A amp B Zero time plasma drug concentration intercepts of biphasic
intravenous disposition curve The coefficient B is based on the terminal exponential phase
(μgml) α amp β Hybrid rate constant of biphasic intravenous disposition curve values of α
and β are related to the slopes of distribution and elimination phase respectively of
biexponential drug disposition curve (h-1
) T05 (α) Distribution half ndash life (h) t05 (β)
Elimination half ndash life (h) K12 First ndash order transfer rate constant for drug distribution from
Central to peripheral compartment (h-1
) K21 First order transfer rate constant for drug
distribution from Peripheral to central compartment (h-1
) Vdss The apparent volume of
distribution which was calculated by steady ndash state method (mlkg) AUMC Area under
moment curve MRT Mean residence time AUC Total area under the serum drug
concentration versus time curve from t = 0 to t = α after administration of a single dose F
Bioavailability Cmax maximum drug concentration Tmax time of maximum observed
concentration in blood
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Figure (1) Arthimatic plot of Serum concentrations of ceftriaxone (μgml) in normal
goats following a single intramuscular injection )diamsdiams( previously given the same doseby
a single intravenous injection () of 20 mg ceftriaxonekgbwt (n=4)
Figure (2) Semilogarthmic graph depicting the time course of ceftriaxone in serum of
normal goats following repeated ntramuscular injection of 20 mg ceftriaxonekgbwt
twice dialy for five consecutive days (n=4)
Figure (3) Semilogarthmic graph depicting the time course of ceftriaxone in serum of
experimentally Salmonella typhimurim infected goats following repeated ntramuscular
injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4) 3
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Table (2) Pharmacokinetic parameters of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected
goats following repeated ntramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)
Dose
Unit
عىهParameters
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1269plusmn0073 7409plusmn121 1352plusmn0132 6373plusmn147 1410plusmn0243 5923plusmn126 1461plusmn0214 5430plusmn125 1424plusmn0172 7635plusmn176 gmlmicro A
0651plusmn0049 plusmn000843116 0720plusmn0008 plusmn00413300 0823plusmn0006 plusmn00263322 0848plusmn0025 plusmn00233323 0786plusmn0028 133plusmn0033 h-1 Α
106plusmn0008 330plusmn0015 0962plusmn0011 0392plusmn0007 0841plusmn0007 0567plusmn012 0818plusmn0024 0569plusmn0012 0885plusmn0030 plusmn00124322 H T05(α)
248plusmn0019 168plusmn0047 203plusmn0075 181plusmn0033 267plusmn0039 120plusmn0028 248plusmn0060 122plusmn0026 222plusmn0100 136plusmn0027 h-1 Kab
0278plusmn0002 0412plusmn0009 0342plusmn0012 0383plusmn0008 0252plusmn0009 0567plusmn0011 0279plusmn0005 00569plusmn0011 0314plusmn0014 0 510plusmn0012 H T05(ab)
0627plusmn0008 0378plusmn0007 0430plusmn0008 0402plusmn0008 0113plusmn00027 0424plusmn0009 0117plusmn0004 0394plusmn0008 0116plusmn0003 0239plusmn0005 h-1 K12
121plusmn0013 0962plusmn0022 141plusmn0021 130plusmn0023 0666plusmn0019 0651plusmn0013 0683plusmn0020 0660plusmn0013 0761plusmn0039 0998plusmn0023 h-1 K21
115plusmn0035 129plusmn0026 104plusmn0047 112plusmn0024 106plusmn0037 122plusmn0025 110plusmn0077 119plusmn0023 0910plusmn0032 123plusmn0023 H Tmax
4182plusmn0628 6108plusmn140 3440plusmn0363 5135plusmn0860 3117plusmn0965 4774plusmn0854 2713plusmn0781 4243plusmn0 870 2479plusmn0547 4065plusmn0825 gmlmicro Cmax
4944plusmn0820 7195plusmn142 4199plusmn0702 6511plusmn130 3190plusmn0688 5117plusmn113 3185plusmn0909 4709plusmn0990 3256plusmn0918 6329plusmn139 gmlmicro B
0164plusmn0003 0189plusmn00043 0181plusmn0002 0178plusmn0004 0181plusmn00035 0167plusmn0004 0214plusmn0009 0195plusmn0005 0249plusmn0918 0272plusmn0006 h-1 β
423plusmn0079 367plusmn0086 381plusmn0047 388plusmn0089 382plusmn0074 415plusmn0081 325plusmn0139 355plusmn0075 277plusmn0056 255plusmn0050 H T05β
0879plusmn0015 0429plusmn0009 109plusmn0004 0426plusmn0009 133plusmn0022 0503plusmn0011 154plusmn0064 0675plusmn0013 171plusmn0060 0693plusmn0014 Lkgh Cltot
28358plusmn215 40775plusmn808 21784plusmn0888 34259plusmn720 17860plusmn155 30705plusmn601 15281plusmn239 24135plusmn555 12175plusmn144 20292plusmn487 gmlhmicro AUC
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (3) Milk concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats
following repeated ntramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)
Dose Time of
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
197plusmn0205 200plusmn0408 125plusmn0104 155plusmn0132 0887plusmn0013 0885plusmn014 0500plusmn0040 074plusmn0012 ------------ ------ Before
200plusmn0408 22plusmn0108 197plusmn0205 200plusmn0408 155plusmn0132 197plusmn0205 100plusmn000 155plusmn0132 ----------- -------- 050
526plusmn0166 700plusmn0408 300plusmn0408 64plusmn0163 25plusmn0204 600plusmn0408 155plusmn0132 582plusmn0118 100plusmn000 520plusmn0166 1
640plusmn0163 900plusmn0408 582plusmn0118 792plusmn0114 582plusmn0118 755plusmn0221 275plusmn0061 700plusmn0408 200plusmn0408 691plusmn0176 2
900plusmn0408 1512plusmn0125 640plusmn0163 1475plusmn0322 640plusmn0163 1400plusmn0408 600plusmn0408 1352plusmn0205 526plusmn166 1225plusmn0595 4
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350plusmn0353 400plusmn0408 300plusmn0408 392plusmn0125 300plusmn0408 35plusmn0353 275plusmn006 300plusmn0408 155plusmn0132 275plusmn0061 6
300 plusmn0408 35plusmn0353 125plusmn0104 200plusmn0408 125plusmn0104 155plusmn01 0825plusmn0062 100plusmn000 0500plusmn0040 0887plusmn0013 8
200plusmn0408 22plusmn0108 100plusmn000 155plusmn0132 100plusmn000 125plusmn0104 0730plusmn002 0825plusmn0078 0422plusmn000 073plusmn0020 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (4) Milkserum concentrations ratios of ceftriaxone in normal and experimentally Salmonella typhimurim infected
goats following repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice daily for five consecutive days (n=4)
Dose Time of
a
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
0400plusmn0049 025plusmn0063 0307plusmn0026 021plusmn0019 0365plusmn00064 016plusmn0026 0232plusmn0016 0205plusmn0002 -------- helliphelliphelliphellip Before
0057plusmn0125 0042plusmn00025 0062plusmn00062 0042plusmn0010 0575plusmn00062 0055plusmn0006 0067plusmn0016 0049plusmn0005 --------- -------- 050
0127plusmn00062 0115plusmn00064 008plusmn0012 0117plusmn0004 0088plusmn00054 0122plusmn0008 008plusmn0017 0126plusmn0028 0039plusmn0005 0122plusmn0004 1
018plusmn0008 0185plusmn0010 021plusmn0004 017plusmn0004 0182plusmn0054 0179plusmn0006 0112plusmn00025 0193plusmn0012 0097plusmn0020 019plusmn0004 2
0357plusmn0020 0425plusmn0005 033plusmn0021 045plusmn0009 0285plusmn0082 0494plusmn0015 0395plusmn0016 0572plusmn001 0415plusmn0017 054plusmn0027 4
018plusmn0015 016plusmn0016 0207plusmn0022 0175plusmn0006 0257plusmn0037 0180plusmn0017 0272plusmn0015 0201plusmn003 0196plusmn0016 0222plusmn0002 6
0212plusmn0033 0212plusmn0020 0200plusmn0044 0122plusmn0024 0152plusmn0011 014plusmn0022 0122plusmn00062 0102plusmn0001 0107plusmn00094 0117plusmn0002 8
0372plusmn0042 025plusmn001 0325plusmn0027 0192plusmn0014 0265plusmn00064 0185plusmn0015 0272plusmn0125 0195plusmn0012 0252plusmn0032 0275plusmn0009 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
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Table (5) The amount of urine (mlmin) voided in normal and experimentally Salmonella typhimurim infected goats following
repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)
Dose Time of a
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
plusmn00372344 126plusmn0034 130plusmn0030 130plusmn0028 118plusmn0066 118plusmn0067 108plusmn0013 108plusmn0008 ----------- -------- Before
0577plusmn0069 43494057plusmn 045plusmn0060 plusmn0064309 0312plusmn002 033plusmn0012 0340plusmn0024 033plusmn0012 0287plusmn0017 0272plusmn0014 050
0712plusmn0019 0692plusmn0014 068plusmn0081 0697plusmn0006 0672plusmn0011 0675plusmn 0009 0635plusmn0032 0655plusmn0010 0719plusmn0031 0697plusmn0015 1
0837plusmn0025 0787plusmn0021 0732plusmn0011 plusmn00054300 0715plusmn0011 0715plusmn002 0722plusmn0019 0702plusmn0018 0737plusmn0027 0762plusmn0041 2
0535plusmn0095 0507plusmn0021 0447plusmn0022 0452plusmn002 0402plusmn0075 0405plusmn0011 0400plusmn0057 0397plusmn0009 0380plusmn0004 038plusmn001 4
0437plusmn00094 0432plusmn0008 0400plusmn0010 0405plusmn0002 0380plusmn0007 plusmn00044319 0372plusmn0047 037plusmn 0007 0350plusmn0005 0365plusmn0006 6
0397plusmn0028 0410plusmn0008 0380plusmn0012 0395plusmn0009 0355plusmn0086 0352plusmn0007 0340plusmn0004 0345plusmn0005 0302plusmn0004 0335plusmn0005 8
0385plusmn001 0380plusmn0010 0385plusmn00064 0380plusmn0008 0365plusmn0064 0367plusmn0004 0362plusmn0086 0372plusmn0106 0327plusmn0006 0362plusmn0016 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (6) Urine concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats
following repeated intramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)
Dose Time of a
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1125plusmn150 1125plusmn15 735plusmn287 81plusmn324 183plusmn03 555plusmn798 37plusmn0811 1815plusmn43290 -------------- ------ Before
2415plusmn357 2625plusmn374 1695plusmn788 249plusmn574 10575plusmn64 2415plusmn357 5400plusmn273 2085plusmn991 102plusmn160 168plusmn547 050
26025plusmn787 2923plusmn479 22425plusmn1225 2805plusmn35 1695plusmn618 2705plusmn471 10200plusmn547 2415plusmn357 6975plusmn225 22425plusmn894 1
29295plusmn765 3012plusmn346 28575plusmn738 2964plusmn415 2355plusmn259 2923plusmn479 1635plusmn561 2645plusmn917 102plusmn547 24825plusmn616 2
23475plusmn430 2482plusmn616 23475plusmn1564 2415plusmn357 1695plusmn788 198plusmn848 8475plusmn309 1515plusmn708 60plusmn212 1185plusmn45 4
1905plusmn45 2355plusmn259 153plusmn519 1935plusmn960 114plusmn948 159plusmn173 6675plusmn309 1215plusmn45 1312plusmn0552 855plusmn193 6
153plusmn1024 1965plusmn135 1335plusmn1229 150plusmn34 735plusmn295 1365plusmn665 6181plusmn339 72plusmn244 907plusmn0951 5025plusmn143 8
135plusmn519 120plusmn346 11725plusmn1551 96plusmn874 525plusmn295 75plusmn173 153plusmn130 39plusmn212 3735plusmn0458 13125plusmn0552 12
Between normal and diseased
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Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (7) Urineserum concentrations ratios of ceftriaxone following repeated ntramuscular injection of 20 mg
ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats
(n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
229plusmn 163 1448plusmn0743 1885plusmn159 1125plusmn0484 533plusmn0260 1050plusmn358 175plusmn0380 4146plusmn116 ------- ------ Before
741plusmn0063 plusmn01553 58plusmn0242 plusmn0149390 422plusmn0206 683plusmn0106 245plusmn0092 667plusmn0306 0510plusmn0081 559plusmn0181 050
651plusmn0243 plusmn0065031 637plusmn0373 plusmn014431 565plusmn0243 plusmn0085300 360plusmn0303 plusmn0110312 279plusmn0121 534plusmn0248 1
836plusmn0150 plusmn00476322 862plusmn0180 plusmn010463 942plusmn0166 plusmn0130631 217plusmn0303 727plusmn0256 508plusmn0186 plusmn01680340 2
939plusmn0235 plusmn01580344 1006plusmn0710 plusmn00750310 999plusmn0542 plusmn02850344 565plusmn0223 641plusmn0241 48plusmn0164 plusmn014834 4
1005plusmn0418 2plusmn018813 1097plusmn0641 plusmn03979300 993plusmn0921 plusmn0252931 619plusmn0483 plusmn0362933 167plusmn0101 642plusmn0644 6
1091plusmn0649 plusmn075332339 1171plusmn0980 995plusmn0415 925plusmn0593 plusmn05593433 886plusmn0408 plusmn02510311 2055plusmn0311 plusmn02046310 8
2392plusmn129 plusmn032731396 1794plusmn0228 1222plusmn124 1418plusmn109 plusmn026733336 580plusmn0397 plusmn03951326 227plusmn0452 plusmn02740316 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (8) Creatinine clearance (mlmin10kgbwt) following repeated intramuscular injection of 20 mg ceftriaxonekgbwt
twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats (n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1115plusmn0703 2265plusmn167 481plusmn0409 672plusmn0817 669plusmn0672 1202plusmn0777 695plusmn0634 1724plusmn179 ----------- ------ Before
0703plusmn0091 147plusmn0305 0718plusmn0141 251plusmn0707 0547plusmn0055 0699plusmn0092 0802plusmn0099 103plusmn0106 295plusmn0124 0458plusmn0037 050
101plusmn0075 161plusmn0093 131plusmn0099 264plusmn0217 161plusmn0146 373plusmn0499 247plusmn0110 4755plusmn0582 214plusmn0234 103plusmn0166 1
157plusmn0198 387plusmn0340 173plusmn0501 267plusmn0217 187plusmn0563 287plusmn0499 451plusmn0223 972plusmn105 263plusmn0399 169plusmn0454 2
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184plusmn0095 346plusmn0444 173plusmn0501 436plusmn0599 383plusmn0299 682plusmn0584 328plusmn0253 119plusmn153 123plusmn0057 292plusmn0742 4
221plusmn0242 411plusmn0661 241plusmn0186 663plusmn0584 308plusmn0234 422plusmn0314 353plusmn0393 548plusmn0901 105plusmn0057 264plusmn0294 6
261plusmn0295 476plusmn0339 319plusmn0273 753plusmn0676 106plusmn0207 0773plusmn0049 228plusmn0175 456plusmn0340 206plusmn0160 404plusmn0419 8
310plusmn0218 409plusmn0434 3264plusmn0153 669plusmn0476 209plusmn0189 235plusmn0337 217plusmn0143 377plusmn0342 240plusmn0218 6055plusmn0176 12
Between normal and diseased
Plt 005 Plt001 Plt0001
Table (9) Ceftriaxone clearance (mlmin10kgbwt following repeated intramuscular injection of 20 mg ceftriaxone kgbwt
twice in normal and experimentally Salmonella typhimurim infected goats (n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1048plusmn121 0557plusmn684 895plusmn113 0547plusmn560 238plusmn0222 103plusmn 480 0668plusmn0157 0173plusmn216 -------- ----------- Before
156plusmn0251 43204plusmn3322 0936plusmn0162 43211plusmn3334 0473plusmn0037 43469plusmn43964 0300plusmn0028 43341plusmn080 0190plusmn0137 43400plusmn43642 050
166plusmn0079 43323plusmn3311 157plusmn0178 43419plusmn3301 137plusmn0115 43311plusmn33022 0883plusmn0054 43341plusmn 133 0616plusmn0153 43120plusmn3301 1
254plusmn0272 43361plusmn3391 222plusmn0093 4331plusmn3390 243plusmn0180 43209plusmn3309 183plusmn0149 43310plusmn2340 128plusmn0153 43312plusmn3390 2
181plusmn0136 43339plusmn3316 161plusmn0129 433plusmn3329 144plusmn0100 43412plusmn3349 0821plusmn0072 0063plusmn0977 0654plusmn0065 43400plusmn4306 4
160plusmn0177 43393plusmn336 152plusmn0200 43416plusmn331 135plusmn0118 4332plusmn3322 0897plusmn0052 43304plusmn3330 0212plusmn0022 43460plusmn43112 6
153plusmn0049 43291plusmn234 163plusmn0242 43346plusmn3300 0891plusmn0272 43306plusmn3310 108plusmn0071 43416plusmn04310 0229plusmn0046 43490plusmn43916 8
340plusmn0522 43214plusmn2341 249plusmn0150 43112plusmn3393 186plusmn0159 43320plusmn336 0773plusmn0094 43390plusmn 134 0264plusmn0043 43400plusmn 54369 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
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Table (10) Ceftriaxone clearancecreatinine clearance following repeated ntramuscular injection of 20 mg
ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats
(n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
0934plusmn0083 0305plusmn0013 183plusmn0116 0864plusmn0098 0358plusmn0018 0279plusmn0047 0099plusmn0020 0127plusmn0001 ------- ----------- Before
220plusmn0115 0819plusmn0044 131plusmn00414 0458plusmn0029 0876plusmn0063 126plusmn0068 0361plusmn0011 0813plusmn0031 0018plusmn0003 108plusmn0062 050
164plusmn0078 0818plusmn0029 118plusmn0068 0546plusmn0027 0858plusmn0052 0407plusmn0041 0331plusmn0009 0287plusmn0025 0324plusmn0011 0909plusmn0187 1
161plusmn0044 0488plusmn0005 232plusmn128 0329plusmn0027 169plusmn0464 0686plusmn0050 0409plusmn0020 0220plusmn0029 0512plusmn0077 266plusmn177 2
0933plusmn0024 0394plusmn0005 0948plusmn0062 0296plusmn0007 0381plusmn0027 0160plusmn0008 0235plusmn0014 0083plusmn0006 0528plusmn0028 0362plusmn0041 4
0726plusmn0018 0411plusmn0028 0639plusmn0066 0204plusmn0006 0446plusmn0034 0286plusmn0008 0238plusmn0019 0214plusmn0006 020plusmn0013 0382plusmn0028 6
0609plusmn0072 0425plusmn0036 0508plusmn0052 0192plusmn0009 0524plusmn0146 174plusmn0083 0477plusmn0015 0213plusmn00018 0109plusmn0185 0222plusmn0006 8
108plusmn0128 0496plusmn0012 0942plusmn0004 0265plusmn0030 0891plusmn0056 0706plusmn0103 0351plusmn0022 0354plusmn0018 0111plusmn0021 0098plusmn0018 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
DISCUSSION
In the present investigation intravenous injection of 20 mg ceftriaxonekgbwt in normal goats the drug showed high serum level
(92plusmn 0408 μgml) at 5 minutes post-injection then its concentration was decreased gradually till reached its minimum level (18
plusmn0816μgml) at 8hours post-injection
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In the present investigation the intravenous injection of 20 mg ceftriaxonekgbwt In normal
goats showed that the drug disposition best fitted a two-compartments- open model a
compartment of plasma and rapid equilibrating tissues and a deeper slower compartment
The obtained result is consistent with those reported for ceftriaxone in lactating goats[9]
lactating ewe[25]
domestic cat[15]
calves[26]
and patanwadi sheep[8]
Also this phenomenon is
in agreement with those reported for other cephalosporines as ceftazidime in a rabbit[27]
cefepime in dog and neonatal foals[28]
ewes[29]
ceftriaxone in goats[9]
cefipime in calves[30]
ceftiofur in cross-bred friesian cattle[31]
cefipime in calves[32]
ceftiofur in cows[33]
cefpirome
in cross-bred calves[3]
cefazidime in goats[35]
and cefquinome in sheep and goats[36]
cefipime
in chickens[37]
Ceftriaxone was distributed after intravenous injection with a distribution phase (α) equal to
656 per hour with a short distribution half ndash life [t05 (α)] equal to 0104 hour The shorter
distribution half-life of ceftriaxone in goats suggested the rapid distribution of the drug in
body tissue and fluid and that nearly similar to that recorded for ceftriaxone in lactating
goats(012 hour)[9]
for ceftriaxone in lactating ewes (0152 hour)[2]
and for ceftriaxone in
calves( 013hour)[26]
The rapid distribution of ceftriaxone in goats is supported by high rate constant of transfer of
the drug from central to peripheral compartment [K12 = 353 h-1
] as compared to the rate
constant of transfer of the drug from peripheral to central compartment [K21= 295 h-1
] This
value is nearly similar to those reported for cefotaxime in goats (K21=327 h-1
)[38]
On contrast
this value was higher than those recorded for ceftriaxone in lactating goats (K21=143 h-1
)[9]
in
lactating ewes (K21=125 h-1
)[25]
and in domestic cats (K21=154 h-1
)[15]
The apparent volume of distribution of ceftriaxone was (0355plusmn0004LKg) this value is
nearly similar to that recorded for cefaronide in sheep(039 LKg)[7]
cefotaxime in dog (048
lkg)[39]
in goat (051 lkg)
[40] for caphalexin in buffalo calves (041 Lkg)
[41] for cefipime in
ewes and calves (032 lkg) (043Lkg)[29]
and[30]
respectively For ceftriaxone in domestic
cats (057Lkg)[15]
in camel (032Lkg)[42]
On the other hand this result is differ than that
reported for cefotaxime in buffalo calves (117Lkg)[43]
High value of the volume of
distribution suggested extensive penetration power Drug with volume of distribution greater
than one literkilogram indicated wide distribution or extensive tissue binding or both[44]
The
apparent volume of distribution in the present study indicated moderate tissue penetrating
power This result agreed with[15]
for ceftriaxone in domestic cats
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Ceftriaxone is eliminated in the current study following a single intravenous injection with
elimination half ndashlife [t 05(β)] equal to 519 hours This observation is nearly agreed with the
data recorded for ceftizoxime in goats (624hours)[45]
On contrast this value was longer than
that reported for ceftriaxone in lactating ewe (175hours)[25]
for cefaronide in sheep (17
hours)[7]
For cephalexin in buffulo calves (216hours)[41]
for ceftriaxone in healthy horse
(162hours)[46]
also this value is longer than that recorded for ceftriaxone in lactating goats
(144hours)[9]
for cefipime in goats (186hours)[47]
The rate of total body clearance of ceftriaxone following a single intravenous injection is
0048 lkgh which equal to data reported for ceftizoxime in lactating goats (005Lkgh)[45]
On contrast this value is lower than that reported for ceftriaxone in buffulo calves lactating
goats buffulo calves (Bubalus bubalis) goats (capra hircus) patanwadi sheep (026 Lkgh)
(395 Lkgh) (440 Lkgh) (450 Lkgh) (391 Lkgh)[12913118]
respectively
The variation in total body clearance might be attributed to specific interspecies variation
handling of the drug method used healthy status of the animal[48]
The difference between values calculated for pharmacokinetic parameters may be attributed
to animal species the drug formulation employed the age the size or sex o l lf the animal
or even inter individual variation and also due to method of analysis of the drug[49]
Following a single intramuscular injection of 20 mg ceftriaxonekg bwt In normal goats the
drug reached its peak serum concentrations after one hour of injection with value
of(41μgml) Ceftriaxone could be detected in serum in a therapeutic level (263μgml) at 12
hours post-injection The reported peak serum concentrations neerly similar to that reported
for cephalexin in buffulo calves (457 microgml)[41]
These results is differed than those reported
for ceftriaxone in cross breed calves (188 microgml at 30 min[16]
in Kangro breed of goats
(Capra Hircus) (2640 microgml at 20 min[10][50]
found after intramuscular administration of
ceforazone peak plasma concentration was (976 microgml) at 45min This result was also higher
than that recorded for ceftriaxone in buffalo calves (158 microgml)[13]
The calculated maximum serum concentration (Cmax) is (40015 microgml) at maximum time
(tmax) of 157 hours The reported (Cmax) agreed with the data reported for cefipime in goats
(4932 microgml[47]
The reported maximum serum concentration (Cmax) is higher than that
reported for ceftriaxone in lactating goats(236 microgml)[9]
in lactating ewes (1722 microgml[25]
in
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
goats (2151 microgml)[11]
for cefquinome in camels (123 microgml)[51]
for ceftriaxone in calves
(1534 microgml)[26]
in patanwadi sheep (1553 microgml)[8]
for cefpirome in cattle (101 microgml)[52]
And for ceftiofur in chickens (2594 μgml)[37]
On the other hand the result was lower than
that reported by[6]
who observed the maximum serum concentration (Cmax) of ceftriaxone in
human after ntramuscular administration was (805 microgml) also it was lower than that
reported for ceftriaxone in dog (11510 microgml)[53]
in domestic cats (5440 microgml)[15]
and for
ceftazoxime in goats (8878 microgml)[45]
The reported [tmax] is neerly similar to that reported for ceftriaxone (104hours)in lactating
ewes by[25]
On contrast it is longer than those reported for ceftriaxone in dogs
(129hours)[53]
for ceftriaxone in lactating goats (07hours)[9]
also the result was longer than
that reported for ceftriaxone in domestic cats (033hours)[15]
in buffulo calves (05 hours)[13]
and for cefpirome in cattle (075hours)[52]
The reported [tmax] is shorter than those reported
for cefquinome in camels (425hours)[51]
in sheep and goats (261 and 262 hours)[36]
and for
ceftiofur in chickens (251 hours)[37]
The elimination half life [t05(β)]
following a single intramuscular administration was 1804 hours This value is nearly agreed
with that recorded for cefquinomein camels (1024hours)[52]
On contrast this result is longer
than that reported for cephalexin in buffalo calves (243hours)[41]
for ceftriaxone in lactating
ewes (177hours)[25]
in buffalo calves (438hours)[13]
in goats (203 hours)[11]
and for
cefipime in goats (165 hours)[47]
The rate of total body clearance of ceftriaxone following a single intramuscular injection is
0043lkgh This value was lower than that reported for ceftriaxone in buffulo calves
(401Lkgh)[13]
in goats (304 Lkgh)[11]
and in sheep (222 Lkgh)[8]
Bioavailability is the fraction of the drug administered by non vascular rout that gains
accesses to the systemic circulation The obtained result revealed that the calculated systemic
bioavailability percent was 6128 It is equal to that recorded for cefpirome in cow calves
(61)[54]
It is nearly equal to that recorded for ceftriaxone in sheep (64)[8]
On the other
hand this value is higher than those recorded for cefperazone in crossbred calves (481)[50]
for ceftriaxone in goats (59)[11]
in calves (47)[55]
On contrast this value is lower than
those reported for cefotaxime in two cats 982 and 93)[57]
for cephradine in goats
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
(739)[58]
for ceftazidime in a rabbit (966)[27]
for ceftriaxone in lactating goats (85)[9]
in lactating ewes (836)[25]
in domestic cats 8572[15]
for cefipime in goats 8645[47]
for ceftriaxone in buffulo calves 702[13]
and for ceftiofur in chickens 8890[37]
Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium
infected goats twics dialy for five days revealed that the drug could be detected in a
therapeutic level for 12hours following repeated intramuscular administrations and exceeded
the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]
The relative higher serum concentrations of ceftriaxone after the last dose compared to the
first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12
hours intervals for five consecutive days These observations agreed with data reported by[36]
on comparing the data of serum levels of repeated intramuscular injections with first
intramuscular injection it was revealed that repeated intramuscular injections of cefquinome
have cumulative effect in both species sheep and goats
The obtained result is inconsistent with that reported by[56]
who found thatwhen cefotaxime
was administered repetitively in patients the ratio of maximal serum levels after the last dose
to those after the first dose demonstrated minimal accumulation of intact drug and by[60]
who
found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in
buffalo calves
The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium
infected goats are significantly lower than those in normal goats following repeated
intramuscular injection These lower blood concentrations in Salmonella typhimurium
infected goats might be attributed to the higher penetrating power of ceftriaxone to the
diseased tissues[48]
This phenomenon is similar to data recorded by[61]
who suggested that
Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of
ceftriaxone These alterations might be due to fever and inflammation induced by
infections[59]
proved that the serum concentrations of cephradine following intramuscular
administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after
each intramuscular dose with a lower significant values recorded in Escherichia-coli infected
goats than in normal goatsAlso similer to that reported by[62]
who observed that the
maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep
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1451
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
in comparison to normal sheepOn contrast[43]
reported that peak plasma level of cefotaxime
in febrile buffalo calves was higher than healthy buffalo calves
In this study the total body clearance (CLtot) in normal goats are significantly lower than in
Salmonella typhimurium infected goats This result supported by[61]
and[63]
fever and
inflammation are cardinal features in bacterial infection which may in turn caused an
increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all
these could lead to increased in the rate at which the drug was delivered to both organs which
were important sites of drug excretion This might somewhat explain the increase in the total
body clearance in infected goats This result is differ than that reported by[64]
who observed
that the clearance of ceftriaxone was significantly reduced in infected mice than in non
infected animals
The highest concentrations of ceftriaxone in milk are recorded 4 hours after each
intramuscular injection with a significant lower value in Salmonella typhimurium infected
goats than in normal goats This might be attributed to accumulation of drug in the inflammed
tissues[48]
This result is similar to those reported by[6559]
who found that milk concentrations
of gentamicin and cephradine were significantly lower in infected goats and cattle than in
normal ones respectively
The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the
non-ionic passive diffusion principle[66]
reported that most drug cross-lipid membranes by
passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly
influenced by the physicochemical properties of the drug[6768]
Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum
ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the
physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]
Milk
contains substantially more lipid and less protein than serum and is slightly more acidic
Therefore drugs which tend to concentrated in milk are weak bases with low serum protein
binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide
and aminothiazole also possesses an hydroxytriazinone group as new and additional
ionization center[70]
these compounds are sufficiently lipid- soluble to be able to penetrate
tissues
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
The dose of ceftriaxone used in the present study induced therapeutically concentrations in
milk These concentrations suggested that ceftriaxone would be efficacious in treatment of
mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily
for 3-5 days
The study showed that the urine concentrations of ceftriaxone are greater than the concurrent
serum concentrations following intramuscular injection This observation is similar to those
reported in cows after cephapirin administrations[71]
In the present study urine concentrations of ceftriaxone increased with the repetition of
dosing This observation supported by[72]
after repeated intramuscular administrations of
ceftriaxone in healthy volunteeres
The mean peak urine concentrations of ceftriaxone were reached 2 hours after each
intramuscular injection The lower urine ceftriaxone concentrations in Salmonella
typhimurium infected goats than in normal goats might be attributed to the accumulation of
the drug in the inflamed tissues[48]
The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower
ratio in Salmonella typhimurium infected goats than in normal goats at different time of
sampling This indicates that glomerular filteration seemed to be the main pathway of
ceftriaxone elimination This observation supported by[59]
who found that the ratio between
cephradine clearance from blood of goats to creatinine clearance showed a marked decrease
in Escherichia-coli infected goats than in normal goats This indicated that glomerular
filteration seemed to be the main pathway of cephradine elimination with a limited rate of
tubular reabsorption
CONCLUSION
The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value
referred a better absorption of ceftriaxone from its site of intramuscular administration The
high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular
administrations suggested that ceftriaxone could be used for treatment of mastitis caused by
Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats
The high concentrations of ceftriaxone in urine after repeated intramuscular administrations
suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections
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1453
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in
goats
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26 Jayesh J M Harshad V G Shailesh K B Urvesh D P and Aswin M T (2010)
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28 Gardner S Y and Papich M G (2001) Comparison of cefepime pharmacokinetics in
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29 Ismail M (2005a) Pharmacokinetics of cefepime administered by iv and im routes to
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30 Patel U D Bhavsar S K and Thaker A M (2006) Pharmacokinetics and dosage
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31 El-Gendy AAM Tohamy MA and Ismail M (2007) Comparative pharmacokinetic
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32 Joshi B and Kumar Sharma S (2009) The pharmacokinetics of cefepime in E coli
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33 Tohamy MA (2008) Pharmacokinetics of ceftiofur sodium administered concomitantly
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34 Rajput N Kumar V D and Sandhu HS (2011) Pharmacokinetics and dosage
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35 Abo-El- Sooud K and Tohamy MA (2011) Comparative pharmacokinetics and milk
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36 El-Hewaity M Abd El Latif A Soliman A and Aboubakr M (2014) Comparative
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37 El-Sayed M G A El-Komy A A A El barawy A M and Ibrahim D M A (2015)
Pharmacokinetics and tissue residues of ceftiofur in normal and Escherichia coli infected
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38 Datta B Mandal TK and Chakraborty A K (2003) Pharmacokinetics of cefotaxime
in goats with experimentally induced kidney damage Ind J pharmacol (35) 173-176
39 Guerrini HV English BP Filippich J L Schneider J and Bourne D W (1986)
The pharmacokinetics of cefotaxime in dog Vet Rec 119(4) 81-83
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40 Atef M Ramadan A Afifi N A and Youssef S A (1990) pharmacokinetic profile
of cefotaxime in goat Res Vet Sci 49(1) 34-38
41 Satish K G Chaudhary RK Srivastiva AK and Garg BD (1990) Pharmacokintics
and dosage regemine of cephalexine in buffulo calves (Bubalis Bubalis following single
intravenous and intramusculer adminsteration Veterinary research commuincation 14
59-62
42 Goudah A (2008) Pharmacokinetic parameters of ceftriaxone after single intravenous
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84(3) 483-9
43 Sharma SK Srivastava AK and Deore DM (2006) Effect of Ecoli
lipopolysaccharides ndashinduced fever on disposition pattern of cefotaxime in buffalo calves
Veterinarski Arhiv 76(6) 537-545
44 Baggot JD (1977) Priniciple of pharmacokinetics In principle of drug disposition in
domestic animals The physiological Basis of veterinary Clinical Pharmacology 1st ed
WB Saunders Co Philadelphi PA 168-179
45 Karmaker UK Datta BK Patra PH Prashant M Suman S Sar TK Chakaborty
AK and mandal KT (2011) Disposition kinetics of ceftizoxime in healthy and mastitic
goats after intravenous adminsteration Pharmacologyonline 3 935-946
46 Ringger NC Pearson EG Gronwall R Kohlepp S J (1996) Pharmacokinetics of
ceftriaxone in healthy horses Equine Vet J Nov 28(6) 476-9
47 Prawez S Raina R Dimitrova D panka NK Ahanger AA Verma PK (2010) The
pharmacokinetics of cefipime in goats following single dose iv and im adminsteration
Turk j vet Anima Sci 34(5) 427-431
48 Baggot JD (1980) Distribution of antimicrobial agents in normal and diseased animals
JAVMA 19(76) 1085-1090
49 Haddad N S Pedersoli W M Ravis W R Fazeli M H and Carson Jr R L (1985)
Pharmacokinetics of gentamicin at steady-state in ponies serum urine and endometrial
concentrations Am J Vet Res 46(6) 1268-1271
50 Gupta JK Chaudhary RK and Dumka VK (2008) Pharmacokinetics after single
intramuscuker adminsrerarion and in-vitro binding plasma protein of cefoprazone in cross
bred calves Veterinaski Arhiv 78(5) 441-448
51 Al Taher AY (2010) Pharmacokinetics of cefquinome in camels J An Vet Ad 9(4)
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52 Rajput N Dumka V K and Sandhu HS (2012) Pharmacokinetics and in- vitro
plasma protein binding of cefpirome in cattle Veterinaski Arhiv 82(1) 1-9
53 RebueltoM Albarellos G Ambros L Kreil V Montoya L Bonafine R Otero P
Hallu R (2002) Pharmacokinetics of ceftriaxone administered by the intravenous
intramuscular or subcutaneous routes to dogs J Vet Pharmacol Ther Feb 25(1) 73-6
54 Patel RB Bhavsar SK Solanki PF Patel JH Varia RD Modi Falguni D and
Patel MD (2013) Pharmacokinetics of cefpirome following intravenous and
intramuscular administration in cow calves Sci Int 1(11) 371-374
55 Maradiya J J Goriya H V Bhavsar S K Patel U D and Thaker A M (2010)
Pharmacokinetics of ceftriaxone in calves Veterinarski arhiv 80(1) 1-9
56 Inges R MJ Fillastre J Godin M Leroy A and Humbert G (1982) The
Pharmacokinetics of cefotaxime and its metabolites in subjects with normal and impaired
renal function Clin Infect Dis (4) 379-391
57 Mcelroy D Ravis W R and Clark C H (1986) Pharmacokinetics of cefotaxime in
the domestic cats Am J Vet Res 47(1) 86-88
58 El-Sayed MG Atef M and El-Komy AA (1994) Disposition kinetic of cephradine in
normal and Escherichia coli infected goats Dtsch Tierarztl Wochenschr 101(2) 56-60
59 Soback S and Ziv G (1988) Pharmacokinetics and bioavailability of ceftriaxone
administered intravenously and intramuscularly to calves Am J Vet Res 49 535-538
60 Sharma S K and Srivastava A K (2003) Cefotaxime pharmacokinetics in male
buffalo calves following multiple dosing Veterinarski arhiv 73(4) 191-197
61 Abdulgafar O J Shaibu O B and Emmanuel U E (2011) Effect of Salmonella
typhymurium infection on the pharmacokinetics of ceftriaxone in sokoto red goats Niger
J Basic Applied Sci 19(1) 49-54
62 Ranjan R Birendra K R Amita R and Sanjeet K S (2011) Effect of Effect of E coli E
coli endotoxin induced fever on the pharmacokinetic profile and dosage regimen of
ceftriaxone in sheep (Ovis aries) Veterinarski arhiv 81(4) 423-432
63 Etuk EU and Onyeyili PA (2006) The effect of Salmonella infection on the plasma
kinetic of chloramphenicol in the sokoto red goats Inter J Pharmacol 2(1) 28-32
64 Wang E Bergeron Y and Bergeron MG (2005) Ceftriaxone pharmacokinetics in
interleukin-10-treated murine pneumococcal pneumonia J Antimicrob Chemother 55
721ndash726
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
65 El-Sayed MG Hatem ME and El-Komy AA (1989) Disposition kinetic of
gentamicin in normal and endometric cow using microbiological assay Dtsch Tierarztl
Wochenschr 96(8) 412-415
66 Aramyona JJ Mora J Fraile LJ Garcia MA Abadia AR and Breganate MA
(1996) Penetration of enrofloxacin and ciprofloxacin into breast milk and
pharmacokinetics of the drugs in lacating rabbits and neonatal offspring Am J Vet Res
57(4) 547-553
67 Rusmussen F (1966) Studies on the mammary excretion and absorbtion of drugs Vet
Rec (87) 14-18
68 Alkinson A and Begg E (1990) Prediction of drug distribution into human milk from
physicochemical characteristics Clin Pharmacokinet 18(2) 151-167
69 Kenneth F (1997) Drug distribution in human milk Aust Prescr 20(2) 35-40
70 Aleksić M Savić V Popović G Burić N and Kapetanović V (2005) Acidity
constants of cefetamet cefotaxime and ceftriaxone the effect of the substituent at C3
position J Pharm Biomed Anal 39(3-4) 752-756
71 Prades M Brown M P Gronwall R and Miles N S (1988) Pharmacokinetics of
sodium cephapirin in lactating dairy cows Am J Vet Res 49(11) 1888-1890
72 Holazo A A Patel I H Weinfeld R E Konikoff J J and Parsonnet M (1986)
Ceftriaxone pharmacokinetics following multiple intramuscular dosing Euro J Clin
Pharmacol 30(1) 109-112
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
Assay of samples
According to[20]
three plates were used for each sample Six pores were made three of them
were filled with reference concentration while the other three pores were filled with the
serum milk or urine samples in triplicate manner The plates were incubated at 37degC for 18
hours then the diameter of inhibitory zones were measured The diameter of inhibitory zones
of samples were corrected by using the zone diameter of the reference concentration in the
same manner as previously discussed either by addition or subtraction From the standard
curve the concentrations corresponding to the corrected values of the inhibitory zones were
obtained
Drug clearance
Clearance of the tested drug from the blood of goats was estimated according to the following
equation
Drug clearance10 kg b wt =
Drug concentration in urine (microgml) X rate of diuresis (mlmin) Body weight (Kg)
_________________________________________________________________
Drug concentration in serum (microgml) X 10
Assay of creatinine in serum and urine
Creatinine was assayed by[21]
and performed by kit manufactured by Diamond diagnostics
company
Creatinine clearance
The creatinine clearance (mlmin10 kgbwt) for goats was calculated by the following
equation
Creatinine clearance 10 kgbwt =
Creatinine concentration in urine (mgL) X rate of diuresis (mlmin) Body weight (Kg)
______________________________________________________________________
Creatinine concentration in serum (mgL) X 10
Pharmacokinetic analysis
The pharmacokinetic parameters were calculated by using Winonlin version 12 and other
parameters according to[2223]
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
Statistical Analysis
The data were calculated as mean plusmn standard error All statistical analysis were carried out
according to[24]
using the scientific calculator CASIO fx 120
RESULTS
Following a single intravenous injection of 20 mg ceftriaxonekg bwt in normal goats
ceftriaxone could be detected therapeutically for 8 hours post intravenous injection The
serum concentration ndash time curve of ceftriaxone following intravenous injection showed that
the drug obeyed a two compartments open model (Figure 1) The disposition kinetics of
ceftriaxone following a single intravenous intramuscular injection were recorded in table (1)
Intramuscular injection of 20 mg ceftriaxone per kilogram body weight twice daily for five
consecutive days in normal and Salmonella typhimurium infected goats revealed a lower
significant serum ceftriaxone concentration after the first third fifth seventh ninth doses in
Salmonella typhimurium infected goats compared with normal goats The pharmacokinetic
parameters of ceftriaxone after repeated intramuscular injection in normal were compared to
those in Salmonella typhimurium infected goats (Table 2) and (Figure 2 amp 3)
The highest concentrations of ceftriaxone in milk were recorded 4 hours after each
intramuscular dose (Table 3) with a significant lower value in Salmonella typhimurium
infected goats compared with normal goats The calculated milkserum concentrations ratios
of ceftriaxone after repeated intramuscular injection (Table 4)
The amount of urine (mlmin) voided after repeated intramuscular injection of 20 mgkg bwt
Twice daily of ceftriaxone for five consecutive days in normal and experimentally
Salmonella typhimurium infected goats were recorded in table (5) The mean peak urine
concentrations of ceftriaxone (Table 6) were reached 2 hours after each intramuscular dose
with a lower significant concentration in Salmonella typhimurium infected goats compared
with normal goats Urineserum concentration ratios of ceftriaxone after repeated
intramuscular injection in normal and experimentally Salmonella typhimurium infected goats
were calculated and illustrated in table (7) Creatinine clearance (mlmin10 kg bwt)
expressing glomerular filtration rate from blood of goats was shown in table (8) The rate of
ceftriaxone clearance (mlmin10 kg bwt) from blood of goats was shown in table (9) The
ratio between ceftriaxone clearance and creatinine clearance was calculated and illustrated in
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
table (10) The data revealed a significant lower ratio in Salmonella typhimurium infected
goats compared with normal goats after the third fifth seventh ninth doses
Table (1) Pharmacokinetics parameters of ceftriaxone (μgml) following a single
intravenous and intramuscuer injection of 20 mgkg bwt in normal goats (n=4)
Intramusculer_
(XplusmnS E)
Intravenous_
(XplusmnS E) Unit Parameters
-------- 1213 plusmn321321 microgml Cdeg
4360plusmn12343 61390 plusmn330 microgml A
43440plusmn43660 636 plusmn43316 h-1
α
43433plusmn3340 43340 plusmn43442 H (α) 43 T
43420plusmn43233 4333plusmn131 h-1
K12
43446plusmn43400 43409plusmn231 h-1
K21
-------- 43440plusmn431 lkg Vdss
4321plusmn6340 43636plusmn1303 microgml B
434446plusmn43419 43443plusmn43136 h-1
β
43141plusmn39340 43411plusmn331 H t05(β))
4344plusmn43401 434440plusmn43409 lkgh Cl tot
-------- 1136plusmn2111300 microgmlh AUMC
-------- 43303 plusmn0314 H MRT
9300plusmn2439 30plusmn034330 microgmlh AUC
3392plusmn63329 -------- F
43436plusmn4361 -------- h-1
K01
43420plusmn3346 -------- h-1
T05(k01)
4342plusmn330 -------- H Tmax(calc))
43021plusmn04343 -------- μgml Cmax(calc)
Cdeg Drug concentration in the serum at zero time immediately after a single intravenous
injection (μgml) A amp B Zero time plasma drug concentration intercepts of biphasic
intravenous disposition curve The coefficient B is based on the terminal exponential phase
(μgml) α amp β Hybrid rate constant of biphasic intravenous disposition curve values of α
and β are related to the slopes of distribution and elimination phase respectively of
biexponential drug disposition curve (h-1
) T05 (α) Distribution half ndash life (h) t05 (β)
Elimination half ndash life (h) K12 First ndash order transfer rate constant for drug distribution from
Central to peripheral compartment (h-1
) K21 First order transfer rate constant for drug
distribution from Peripheral to central compartment (h-1
) Vdss The apparent volume of
distribution which was calculated by steady ndash state method (mlkg) AUMC Area under
moment curve MRT Mean residence time AUC Total area under the serum drug
concentration versus time curve from t = 0 to t = α after administration of a single dose F
Bioavailability Cmax maximum drug concentration Tmax time of maximum observed
concentration in blood
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Figure (1) Arthimatic plot of Serum concentrations of ceftriaxone (μgml) in normal
goats following a single intramuscular injection )diamsdiams( previously given the same doseby
a single intravenous injection () of 20 mg ceftriaxonekgbwt (n=4)
Figure (2) Semilogarthmic graph depicting the time course of ceftriaxone in serum of
normal goats following repeated ntramuscular injection of 20 mg ceftriaxonekgbwt
twice dialy for five consecutive days (n=4)
Figure (3) Semilogarthmic graph depicting the time course of ceftriaxone in serum of
experimentally Salmonella typhimurim infected goats following repeated ntramuscular
injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4) 3
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Table (2) Pharmacokinetic parameters of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected
goats following repeated ntramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)
Dose
Unit
عىهParameters
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1269plusmn0073 7409plusmn121 1352plusmn0132 6373plusmn147 1410plusmn0243 5923plusmn126 1461plusmn0214 5430plusmn125 1424plusmn0172 7635plusmn176 gmlmicro A
0651plusmn0049 plusmn000843116 0720plusmn0008 plusmn00413300 0823plusmn0006 plusmn00263322 0848plusmn0025 plusmn00233323 0786plusmn0028 133plusmn0033 h-1 Α
106plusmn0008 330plusmn0015 0962plusmn0011 0392plusmn0007 0841plusmn0007 0567plusmn012 0818plusmn0024 0569plusmn0012 0885plusmn0030 plusmn00124322 H T05(α)
248plusmn0019 168plusmn0047 203plusmn0075 181plusmn0033 267plusmn0039 120plusmn0028 248plusmn0060 122plusmn0026 222plusmn0100 136plusmn0027 h-1 Kab
0278plusmn0002 0412plusmn0009 0342plusmn0012 0383plusmn0008 0252plusmn0009 0567plusmn0011 0279plusmn0005 00569plusmn0011 0314plusmn0014 0 510plusmn0012 H T05(ab)
0627plusmn0008 0378plusmn0007 0430plusmn0008 0402plusmn0008 0113plusmn00027 0424plusmn0009 0117plusmn0004 0394plusmn0008 0116plusmn0003 0239plusmn0005 h-1 K12
121plusmn0013 0962plusmn0022 141plusmn0021 130plusmn0023 0666plusmn0019 0651plusmn0013 0683plusmn0020 0660plusmn0013 0761plusmn0039 0998plusmn0023 h-1 K21
115plusmn0035 129plusmn0026 104plusmn0047 112plusmn0024 106plusmn0037 122plusmn0025 110plusmn0077 119plusmn0023 0910plusmn0032 123plusmn0023 H Tmax
4182plusmn0628 6108plusmn140 3440plusmn0363 5135plusmn0860 3117plusmn0965 4774plusmn0854 2713plusmn0781 4243plusmn0 870 2479plusmn0547 4065plusmn0825 gmlmicro Cmax
4944plusmn0820 7195plusmn142 4199plusmn0702 6511plusmn130 3190plusmn0688 5117plusmn113 3185plusmn0909 4709plusmn0990 3256plusmn0918 6329plusmn139 gmlmicro B
0164plusmn0003 0189plusmn00043 0181plusmn0002 0178plusmn0004 0181plusmn00035 0167plusmn0004 0214plusmn0009 0195plusmn0005 0249plusmn0918 0272plusmn0006 h-1 β
423plusmn0079 367plusmn0086 381plusmn0047 388plusmn0089 382plusmn0074 415plusmn0081 325plusmn0139 355plusmn0075 277plusmn0056 255plusmn0050 H T05β
0879plusmn0015 0429plusmn0009 109plusmn0004 0426plusmn0009 133plusmn0022 0503plusmn0011 154plusmn0064 0675plusmn0013 171plusmn0060 0693plusmn0014 Lkgh Cltot
28358plusmn215 40775plusmn808 21784plusmn0888 34259plusmn720 17860plusmn155 30705plusmn601 15281plusmn239 24135plusmn555 12175plusmn144 20292plusmn487 gmlhmicro AUC
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (3) Milk concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats
following repeated ntramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)
Dose Time of
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
197plusmn0205 200plusmn0408 125plusmn0104 155plusmn0132 0887plusmn0013 0885plusmn014 0500plusmn0040 074plusmn0012 ------------ ------ Before
200plusmn0408 22plusmn0108 197plusmn0205 200plusmn0408 155plusmn0132 197plusmn0205 100plusmn000 155plusmn0132 ----------- -------- 050
526plusmn0166 700plusmn0408 300plusmn0408 64plusmn0163 25plusmn0204 600plusmn0408 155plusmn0132 582plusmn0118 100plusmn000 520plusmn0166 1
640plusmn0163 900plusmn0408 582plusmn0118 792plusmn0114 582plusmn0118 755plusmn0221 275plusmn0061 700plusmn0408 200plusmn0408 691plusmn0176 2
900plusmn0408 1512plusmn0125 640plusmn0163 1475plusmn0322 640plusmn0163 1400plusmn0408 600plusmn0408 1352plusmn0205 526plusmn166 1225plusmn0595 4
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350plusmn0353 400plusmn0408 300plusmn0408 392plusmn0125 300plusmn0408 35plusmn0353 275plusmn006 300plusmn0408 155plusmn0132 275plusmn0061 6
300 plusmn0408 35plusmn0353 125plusmn0104 200plusmn0408 125plusmn0104 155plusmn01 0825plusmn0062 100plusmn000 0500plusmn0040 0887plusmn0013 8
200plusmn0408 22plusmn0108 100plusmn000 155plusmn0132 100plusmn000 125plusmn0104 0730plusmn002 0825plusmn0078 0422plusmn000 073plusmn0020 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (4) Milkserum concentrations ratios of ceftriaxone in normal and experimentally Salmonella typhimurim infected
goats following repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice daily for five consecutive days (n=4)
Dose Time of
a
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
0400plusmn0049 025plusmn0063 0307plusmn0026 021plusmn0019 0365plusmn00064 016plusmn0026 0232plusmn0016 0205plusmn0002 -------- helliphelliphelliphellip Before
0057plusmn0125 0042plusmn00025 0062plusmn00062 0042plusmn0010 0575plusmn00062 0055plusmn0006 0067plusmn0016 0049plusmn0005 --------- -------- 050
0127plusmn00062 0115plusmn00064 008plusmn0012 0117plusmn0004 0088plusmn00054 0122plusmn0008 008plusmn0017 0126plusmn0028 0039plusmn0005 0122plusmn0004 1
018plusmn0008 0185plusmn0010 021plusmn0004 017plusmn0004 0182plusmn0054 0179plusmn0006 0112plusmn00025 0193plusmn0012 0097plusmn0020 019plusmn0004 2
0357plusmn0020 0425plusmn0005 033plusmn0021 045plusmn0009 0285plusmn0082 0494plusmn0015 0395plusmn0016 0572plusmn001 0415plusmn0017 054plusmn0027 4
018plusmn0015 016plusmn0016 0207plusmn0022 0175plusmn0006 0257plusmn0037 0180plusmn0017 0272plusmn0015 0201plusmn003 0196plusmn0016 0222plusmn0002 6
0212plusmn0033 0212plusmn0020 0200plusmn0044 0122plusmn0024 0152plusmn0011 014plusmn0022 0122plusmn00062 0102plusmn0001 0107plusmn00094 0117plusmn0002 8
0372plusmn0042 025plusmn001 0325plusmn0027 0192plusmn0014 0265plusmn00064 0185plusmn0015 0272plusmn0125 0195plusmn0012 0252plusmn0032 0275plusmn0009 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
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Table (5) The amount of urine (mlmin) voided in normal and experimentally Salmonella typhimurim infected goats following
repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)
Dose Time of a
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
plusmn00372344 126plusmn0034 130plusmn0030 130plusmn0028 118plusmn0066 118plusmn0067 108plusmn0013 108plusmn0008 ----------- -------- Before
0577plusmn0069 43494057plusmn 045plusmn0060 plusmn0064309 0312plusmn002 033plusmn0012 0340plusmn0024 033plusmn0012 0287plusmn0017 0272plusmn0014 050
0712plusmn0019 0692plusmn0014 068plusmn0081 0697plusmn0006 0672plusmn0011 0675plusmn 0009 0635plusmn0032 0655plusmn0010 0719plusmn0031 0697plusmn0015 1
0837plusmn0025 0787plusmn0021 0732plusmn0011 plusmn00054300 0715plusmn0011 0715plusmn002 0722plusmn0019 0702plusmn0018 0737plusmn0027 0762plusmn0041 2
0535plusmn0095 0507plusmn0021 0447plusmn0022 0452plusmn002 0402plusmn0075 0405plusmn0011 0400plusmn0057 0397plusmn0009 0380plusmn0004 038plusmn001 4
0437plusmn00094 0432plusmn0008 0400plusmn0010 0405plusmn0002 0380plusmn0007 plusmn00044319 0372plusmn0047 037plusmn 0007 0350plusmn0005 0365plusmn0006 6
0397plusmn0028 0410plusmn0008 0380plusmn0012 0395plusmn0009 0355plusmn0086 0352plusmn0007 0340plusmn0004 0345plusmn0005 0302plusmn0004 0335plusmn0005 8
0385plusmn001 0380plusmn0010 0385plusmn00064 0380plusmn0008 0365plusmn0064 0367plusmn0004 0362plusmn0086 0372plusmn0106 0327plusmn0006 0362plusmn0016 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (6) Urine concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats
following repeated intramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)
Dose Time of a
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1125plusmn150 1125plusmn15 735plusmn287 81plusmn324 183plusmn03 555plusmn798 37plusmn0811 1815plusmn43290 -------------- ------ Before
2415plusmn357 2625plusmn374 1695plusmn788 249plusmn574 10575plusmn64 2415plusmn357 5400plusmn273 2085plusmn991 102plusmn160 168plusmn547 050
26025plusmn787 2923plusmn479 22425plusmn1225 2805plusmn35 1695plusmn618 2705plusmn471 10200plusmn547 2415plusmn357 6975plusmn225 22425plusmn894 1
29295plusmn765 3012plusmn346 28575plusmn738 2964plusmn415 2355plusmn259 2923plusmn479 1635plusmn561 2645plusmn917 102plusmn547 24825plusmn616 2
23475plusmn430 2482plusmn616 23475plusmn1564 2415plusmn357 1695plusmn788 198plusmn848 8475plusmn309 1515plusmn708 60plusmn212 1185plusmn45 4
1905plusmn45 2355plusmn259 153plusmn519 1935plusmn960 114plusmn948 159plusmn173 6675plusmn309 1215plusmn45 1312plusmn0552 855plusmn193 6
153plusmn1024 1965plusmn135 1335plusmn1229 150plusmn34 735plusmn295 1365plusmn665 6181plusmn339 72plusmn244 907plusmn0951 5025plusmn143 8
135plusmn519 120plusmn346 11725plusmn1551 96plusmn874 525plusmn295 75plusmn173 153plusmn130 39plusmn212 3735plusmn0458 13125plusmn0552 12
Between normal and diseased
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Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (7) Urineserum concentrations ratios of ceftriaxone following repeated ntramuscular injection of 20 mg
ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats
(n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
229plusmn 163 1448plusmn0743 1885plusmn159 1125plusmn0484 533plusmn0260 1050plusmn358 175plusmn0380 4146plusmn116 ------- ------ Before
741plusmn0063 plusmn01553 58plusmn0242 plusmn0149390 422plusmn0206 683plusmn0106 245plusmn0092 667plusmn0306 0510plusmn0081 559plusmn0181 050
651plusmn0243 plusmn0065031 637plusmn0373 plusmn014431 565plusmn0243 plusmn0085300 360plusmn0303 plusmn0110312 279plusmn0121 534plusmn0248 1
836plusmn0150 plusmn00476322 862plusmn0180 plusmn010463 942plusmn0166 plusmn0130631 217plusmn0303 727plusmn0256 508plusmn0186 plusmn01680340 2
939plusmn0235 plusmn01580344 1006plusmn0710 plusmn00750310 999plusmn0542 plusmn02850344 565plusmn0223 641plusmn0241 48plusmn0164 plusmn014834 4
1005plusmn0418 2plusmn018813 1097plusmn0641 plusmn03979300 993plusmn0921 plusmn0252931 619plusmn0483 plusmn0362933 167plusmn0101 642plusmn0644 6
1091plusmn0649 plusmn075332339 1171plusmn0980 995plusmn0415 925plusmn0593 plusmn05593433 886plusmn0408 plusmn02510311 2055plusmn0311 plusmn02046310 8
2392plusmn129 plusmn032731396 1794plusmn0228 1222plusmn124 1418plusmn109 plusmn026733336 580plusmn0397 plusmn03951326 227plusmn0452 plusmn02740316 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (8) Creatinine clearance (mlmin10kgbwt) following repeated intramuscular injection of 20 mg ceftriaxonekgbwt
twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats (n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1115plusmn0703 2265plusmn167 481plusmn0409 672plusmn0817 669plusmn0672 1202plusmn0777 695plusmn0634 1724plusmn179 ----------- ------ Before
0703plusmn0091 147plusmn0305 0718plusmn0141 251plusmn0707 0547plusmn0055 0699plusmn0092 0802plusmn0099 103plusmn0106 295plusmn0124 0458plusmn0037 050
101plusmn0075 161plusmn0093 131plusmn0099 264plusmn0217 161plusmn0146 373plusmn0499 247plusmn0110 4755plusmn0582 214plusmn0234 103plusmn0166 1
157plusmn0198 387plusmn0340 173plusmn0501 267plusmn0217 187plusmn0563 287plusmn0499 451plusmn0223 972plusmn105 263plusmn0399 169plusmn0454 2
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184plusmn0095 346plusmn0444 173plusmn0501 436plusmn0599 383plusmn0299 682plusmn0584 328plusmn0253 119plusmn153 123plusmn0057 292plusmn0742 4
221plusmn0242 411plusmn0661 241plusmn0186 663plusmn0584 308plusmn0234 422plusmn0314 353plusmn0393 548plusmn0901 105plusmn0057 264plusmn0294 6
261plusmn0295 476plusmn0339 319plusmn0273 753plusmn0676 106plusmn0207 0773plusmn0049 228plusmn0175 456plusmn0340 206plusmn0160 404plusmn0419 8
310plusmn0218 409plusmn0434 3264plusmn0153 669plusmn0476 209plusmn0189 235plusmn0337 217plusmn0143 377plusmn0342 240plusmn0218 6055plusmn0176 12
Between normal and diseased
Plt 005 Plt001 Plt0001
Table (9) Ceftriaxone clearance (mlmin10kgbwt following repeated intramuscular injection of 20 mg ceftriaxone kgbwt
twice in normal and experimentally Salmonella typhimurim infected goats (n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1048plusmn121 0557plusmn684 895plusmn113 0547plusmn560 238plusmn0222 103plusmn 480 0668plusmn0157 0173plusmn216 -------- ----------- Before
156plusmn0251 43204plusmn3322 0936plusmn0162 43211plusmn3334 0473plusmn0037 43469plusmn43964 0300plusmn0028 43341plusmn080 0190plusmn0137 43400plusmn43642 050
166plusmn0079 43323plusmn3311 157plusmn0178 43419plusmn3301 137plusmn0115 43311plusmn33022 0883plusmn0054 43341plusmn 133 0616plusmn0153 43120plusmn3301 1
254plusmn0272 43361plusmn3391 222plusmn0093 4331plusmn3390 243plusmn0180 43209plusmn3309 183plusmn0149 43310plusmn2340 128plusmn0153 43312plusmn3390 2
181plusmn0136 43339plusmn3316 161plusmn0129 433plusmn3329 144plusmn0100 43412plusmn3349 0821plusmn0072 0063plusmn0977 0654plusmn0065 43400plusmn4306 4
160plusmn0177 43393plusmn336 152plusmn0200 43416plusmn331 135plusmn0118 4332plusmn3322 0897plusmn0052 43304plusmn3330 0212plusmn0022 43460plusmn43112 6
153plusmn0049 43291plusmn234 163plusmn0242 43346plusmn3300 0891plusmn0272 43306plusmn3310 108plusmn0071 43416plusmn04310 0229plusmn0046 43490plusmn43916 8
340plusmn0522 43214plusmn2341 249plusmn0150 43112plusmn3393 186plusmn0159 43320plusmn336 0773plusmn0094 43390plusmn 134 0264plusmn0043 43400plusmn 54369 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
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Table (10) Ceftriaxone clearancecreatinine clearance following repeated ntramuscular injection of 20 mg
ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats
(n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
0934plusmn0083 0305plusmn0013 183plusmn0116 0864plusmn0098 0358plusmn0018 0279plusmn0047 0099plusmn0020 0127plusmn0001 ------- ----------- Before
220plusmn0115 0819plusmn0044 131plusmn00414 0458plusmn0029 0876plusmn0063 126plusmn0068 0361plusmn0011 0813plusmn0031 0018plusmn0003 108plusmn0062 050
164plusmn0078 0818plusmn0029 118plusmn0068 0546plusmn0027 0858plusmn0052 0407plusmn0041 0331plusmn0009 0287plusmn0025 0324plusmn0011 0909plusmn0187 1
161plusmn0044 0488plusmn0005 232plusmn128 0329plusmn0027 169plusmn0464 0686plusmn0050 0409plusmn0020 0220plusmn0029 0512plusmn0077 266plusmn177 2
0933plusmn0024 0394plusmn0005 0948plusmn0062 0296plusmn0007 0381plusmn0027 0160plusmn0008 0235plusmn0014 0083plusmn0006 0528plusmn0028 0362plusmn0041 4
0726plusmn0018 0411plusmn0028 0639plusmn0066 0204plusmn0006 0446plusmn0034 0286plusmn0008 0238plusmn0019 0214plusmn0006 020plusmn0013 0382plusmn0028 6
0609plusmn0072 0425plusmn0036 0508plusmn0052 0192plusmn0009 0524plusmn0146 174plusmn0083 0477plusmn0015 0213plusmn00018 0109plusmn0185 0222plusmn0006 8
108plusmn0128 0496plusmn0012 0942plusmn0004 0265plusmn0030 0891plusmn0056 0706plusmn0103 0351plusmn0022 0354plusmn0018 0111plusmn0021 0098plusmn0018 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
DISCUSSION
In the present investigation intravenous injection of 20 mg ceftriaxonekgbwt in normal goats the drug showed high serum level
(92plusmn 0408 μgml) at 5 minutes post-injection then its concentration was decreased gradually till reached its minimum level (18
plusmn0816μgml) at 8hours post-injection
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In the present investigation the intravenous injection of 20 mg ceftriaxonekgbwt In normal
goats showed that the drug disposition best fitted a two-compartments- open model a
compartment of plasma and rapid equilibrating tissues and a deeper slower compartment
The obtained result is consistent with those reported for ceftriaxone in lactating goats[9]
lactating ewe[25]
domestic cat[15]
calves[26]
and patanwadi sheep[8]
Also this phenomenon is
in agreement with those reported for other cephalosporines as ceftazidime in a rabbit[27]
cefepime in dog and neonatal foals[28]
ewes[29]
ceftriaxone in goats[9]
cefipime in calves[30]
ceftiofur in cross-bred friesian cattle[31]
cefipime in calves[32]
ceftiofur in cows[33]
cefpirome
in cross-bred calves[3]
cefazidime in goats[35]
and cefquinome in sheep and goats[36]
cefipime
in chickens[37]
Ceftriaxone was distributed after intravenous injection with a distribution phase (α) equal to
656 per hour with a short distribution half ndash life [t05 (α)] equal to 0104 hour The shorter
distribution half-life of ceftriaxone in goats suggested the rapid distribution of the drug in
body tissue and fluid and that nearly similar to that recorded for ceftriaxone in lactating
goats(012 hour)[9]
for ceftriaxone in lactating ewes (0152 hour)[2]
and for ceftriaxone in
calves( 013hour)[26]
The rapid distribution of ceftriaxone in goats is supported by high rate constant of transfer of
the drug from central to peripheral compartment [K12 = 353 h-1
] as compared to the rate
constant of transfer of the drug from peripheral to central compartment [K21= 295 h-1
] This
value is nearly similar to those reported for cefotaxime in goats (K21=327 h-1
)[38]
On contrast
this value was higher than those recorded for ceftriaxone in lactating goats (K21=143 h-1
)[9]
in
lactating ewes (K21=125 h-1
)[25]
and in domestic cats (K21=154 h-1
)[15]
The apparent volume of distribution of ceftriaxone was (0355plusmn0004LKg) this value is
nearly similar to that recorded for cefaronide in sheep(039 LKg)[7]
cefotaxime in dog (048
lkg)[39]
in goat (051 lkg)
[40] for caphalexin in buffalo calves (041 Lkg)
[41] for cefipime in
ewes and calves (032 lkg) (043Lkg)[29]
and[30]
respectively For ceftriaxone in domestic
cats (057Lkg)[15]
in camel (032Lkg)[42]
On the other hand this result is differ than that
reported for cefotaxime in buffalo calves (117Lkg)[43]
High value of the volume of
distribution suggested extensive penetration power Drug with volume of distribution greater
than one literkilogram indicated wide distribution or extensive tissue binding or both[44]
The
apparent volume of distribution in the present study indicated moderate tissue penetrating
power This result agreed with[15]
for ceftriaxone in domestic cats
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Ceftriaxone is eliminated in the current study following a single intravenous injection with
elimination half ndashlife [t 05(β)] equal to 519 hours This observation is nearly agreed with the
data recorded for ceftizoxime in goats (624hours)[45]
On contrast this value was longer than
that reported for ceftriaxone in lactating ewe (175hours)[25]
for cefaronide in sheep (17
hours)[7]
For cephalexin in buffulo calves (216hours)[41]
for ceftriaxone in healthy horse
(162hours)[46]
also this value is longer than that recorded for ceftriaxone in lactating goats
(144hours)[9]
for cefipime in goats (186hours)[47]
The rate of total body clearance of ceftriaxone following a single intravenous injection is
0048 lkgh which equal to data reported for ceftizoxime in lactating goats (005Lkgh)[45]
On contrast this value is lower than that reported for ceftriaxone in buffulo calves lactating
goats buffulo calves (Bubalus bubalis) goats (capra hircus) patanwadi sheep (026 Lkgh)
(395 Lkgh) (440 Lkgh) (450 Lkgh) (391 Lkgh)[12913118]
respectively
The variation in total body clearance might be attributed to specific interspecies variation
handling of the drug method used healthy status of the animal[48]
The difference between values calculated for pharmacokinetic parameters may be attributed
to animal species the drug formulation employed the age the size or sex o l lf the animal
or even inter individual variation and also due to method of analysis of the drug[49]
Following a single intramuscular injection of 20 mg ceftriaxonekg bwt In normal goats the
drug reached its peak serum concentrations after one hour of injection with value
of(41μgml) Ceftriaxone could be detected in serum in a therapeutic level (263μgml) at 12
hours post-injection The reported peak serum concentrations neerly similar to that reported
for cephalexin in buffulo calves (457 microgml)[41]
These results is differed than those reported
for ceftriaxone in cross breed calves (188 microgml at 30 min[16]
in Kangro breed of goats
(Capra Hircus) (2640 microgml at 20 min[10][50]
found after intramuscular administration of
ceforazone peak plasma concentration was (976 microgml) at 45min This result was also higher
than that recorded for ceftriaxone in buffalo calves (158 microgml)[13]
The calculated maximum serum concentration (Cmax) is (40015 microgml) at maximum time
(tmax) of 157 hours The reported (Cmax) agreed with the data reported for cefipime in goats
(4932 microgml[47]
The reported maximum serum concentration (Cmax) is higher than that
reported for ceftriaxone in lactating goats(236 microgml)[9]
in lactating ewes (1722 microgml[25]
in
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
goats (2151 microgml)[11]
for cefquinome in camels (123 microgml)[51]
for ceftriaxone in calves
(1534 microgml)[26]
in patanwadi sheep (1553 microgml)[8]
for cefpirome in cattle (101 microgml)[52]
And for ceftiofur in chickens (2594 μgml)[37]
On the other hand the result was lower than
that reported by[6]
who observed the maximum serum concentration (Cmax) of ceftriaxone in
human after ntramuscular administration was (805 microgml) also it was lower than that
reported for ceftriaxone in dog (11510 microgml)[53]
in domestic cats (5440 microgml)[15]
and for
ceftazoxime in goats (8878 microgml)[45]
The reported [tmax] is neerly similar to that reported for ceftriaxone (104hours)in lactating
ewes by[25]
On contrast it is longer than those reported for ceftriaxone in dogs
(129hours)[53]
for ceftriaxone in lactating goats (07hours)[9]
also the result was longer than
that reported for ceftriaxone in domestic cats (033hours)[15]
in buffulo calves (05 hours)[13]
and for cefpirome in cattle (075hours)[52]
The reported [tmax] is shorter than those reported
for cefquinome in camels (425hours)[51]
in sheep and goats (261 and 262 hours)[36]
and for
ceftiofur in chickens (251 hours)[37]
The elimination half life [t05(β)]
following a single intramuscular administration was 1804 hours This value is nearly agreed
with that recorded for cefquinomein camels (1024hours)[52]
On contrast this result is longer
than that reported for cephalexin in buffalo calves (243hours)[41]
for ceftriaxone in lactating
ewes (177hours)[25]
in buffalo calves (438hours)[13]
in goats (203 hours)[11]
and for
cefipime in goats (165 hours)[47]
The rate of total body clearance of ceftriaxone following a single intramuscular injection is
0043lkgh This value was lower than that reported for ceftriaxone in buffulo calves
(401Lkgh)[13]
in goats (304 Lkgh)[11]
and in sheep (222 Lkgh)[8]
Bioavailability is the fraction of the drug administered by non vascular rout that gains
accesses to the systemic circulation The obtained result revealed that the calculated systemic
bioavailability percent was 6128 It is equal to that recorded for cefpirome in cow calves
(61)[54]
It is nearly equal to that recorded for ceftriaxone in sheep (64)[8]
On the other
hand this value is higher than those recorded for cefperazone in crossbred calves (481)[50]
for ceftriaxone in goats (59)[11]
in calves (47)[55]
On contrast this value is lower than
those reported for cefotaxime in two cats 982 and 93)[57]
for cephradine in goats
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
(739)[58]
for ceftazidime in a rabbit (966)[27]
for ceftriaxone in lactating goats (85)[9]
in lactating ewes (836)[25]
in domestic cats 8572[15]
for cefipime in goats 8645[47]
for ceftriaxone in buffulo calves 702[13]
and for ceftiofur in chickens 8890[37]
Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium
infected goats twics dialy for five days revealed that the drug could be detected in a
therapeutic level for 12hours following repeated intramuscular administrations and exceeded
the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]
The relative higher serum concentrations of ceftriaxone after the last dose compared to the
first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12
hours intervals for five consecutive days These observations agreed with data reported by[36]
on comparing the data of serum levels of repeated intramuscular injections with first
intramuscular injection it was revealed that repeated intramuscular injections of cefquinome
have cumulative effect in both species sheep and goats
The obtained result is inconsistent with that reported by[56]
who found thatwhen cefotaxime
was administered repetitively in patients the ratio of maximal serum levels after the last dose
to those after the first dose demonstrated minimal accumulation of intact drug and by[60]
who
found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in
buffalo calves
The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium
infected goats are significantly lower than those in normal goats following repeated
intramuscular injection These lower blood concentrations in Salmonella typhimurium
infected goats might be attributed to the higher penetrating power of ceftriaxone to the
diseased tissues[48]
This phenomenon is similar to data recorded by[61]
who suggested that
Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of
ceftriaxone These alterations might be due to fever and inflammation induced by
infections[59]
proved that the serum concentrations of cephradine following intramuscular
administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after
each intramuscular dose with a lower significant values recorded in Escherichia-coli infected
goats than in normal goatsAlso similer to that reported by[62]
who observed that the
maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
in comparison to normal sheepOn contrast[43]
reported that peak plasma level of cefotaxime
in febrile buffalo calves was higher than healthy buffalo calves
In this study the total body clearance (CLtot) in normal goats are significantly lower than in
Salmonella typhimurium infected goats This result supported by[61]
and[63]
fever and
inflammation are cardinal features in bacterial infection which may in turn caused an
increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all
these could lead to increased in the rate at which the drug was delivered to both organs which
were important sites of drug excretion This might somewhat explain the increase in the total
body clearance in infected goats This result is differ than that reported by[64]
who observed
that the clearance of ceftriaxone was significantly reduced in infected mice than in non
infected animals
The highest concentrations of ceftriaxone in milk are recorded 4 hours after each
intramuscular injection with a significant lower value in Salmonella typhimurium infected
goats than in normal goats This might be attributed to accumulation of drug in the inflammed
tissues[48]
This result is similar to those reported by[6559]
who found that milk concentrations
of gentamicin and cephradine were significantly lower in infected goats and cattle than in
normal ones respectively
The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the
non-ionic passive diffusion principle[66]
reported that most drug cross-lipid membranes by
passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly
influenced by the physicochemical properties of the drug[6768]
Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum
ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the
physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]
Milk
contains substantially more lipid and less protein than serum and is slightly more acidic
Therefore drugs which tend to concentrated in milk are weak bases with low serum protein
binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide
and aminothiazole also possesses an hydroxytriazinone group as new and additional
ionization center[70]
these compounds are sufficiently lipid- soluble to be able to penetrate
tissues
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
The dose of ceftriaxone used in the present study induced therapeutically concentrations in
milk These concentrations suggested that ceftriaxone would be efficacious in treatment of
mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily
for 3-5 days
The study showed that the urine concentrations of ceftriaxone are greater than the concurrent
serum concentrations following intramuscular injection This observation is similar to those
reported in cows after cephapirin administrations[71]
In the present study urine concentrations of ceftriaxone increased with the repetition of
dosing This observation supported by[72]
after repeated intramuscular administrations of
ceftriaxone in healthy volunteeres
The mean peak urine concentrations of ceftriaxone were reached 2 hours after each
intramuscular injection The lower urine ceftriaxone concentrations in Salmonella
typhimurium infected goats than in normal goats might be attributed to the accumulation of
the drug in the inflamed tissues[48]
The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower
ratio in Salmonella typhimurium infected goats than in normal goats at different time of
sampling This indicates that glomerular filteration seemed to be the main pathway of
ceftriaxone elimination This observation supported by[59]
who found that the ratio between
cephradine clearance from blood of goats to creatinine clearance showed a marked decrease
in Escherichia-coli infected goats than in normal goats This indicated that glomerular
filteration seemed to be the main pathway of cephradine elimination with a limited rate of
tubular reabsorption
CONCLUSION
The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value
referred a better absorption of ceftriaxone from its site of intramuscular administration The
high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular
administrations suggested that ceftriaxone could be used for treatment of mastitis caused by
Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats
The high concentrations of ceftriaxone in urine after repeated intramuscular administrations
suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in
goats
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38 Datta B Mandal TK and Chakraborty A K (2003) Pharmacokinetics of cefotaxime
in goats with experimentally induced kidney damage Ind J pharmacol (35) 173-176
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40 Atef M Ramadan A Afifi N A and Youssef S A (1990) pharmacokinetic profile
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42 Goudah A (2008) Pharmacokinetic parameters of ceftriaxone after single intravenous
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43 Sharma SK Srivastava AK and Deore DM (2006) Effect of Ecoli
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44 Baggot JD (1977) Priniciple of pharmacokinetics In principle of drug disposition in
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45 Karmaker UK Datta BK Patra PH Prashant M Suman S Sar TK Chakaborty
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49 Haddad N S Pedersoli W M Ravis W R Fazeli M H and Carson Jr R L (1985)
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Pharmacokinetics of cefotaxime and its metabolites in subjects with normal and impaired
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57 Mcelroy D Ravis W R and Clark C H (1986) Pharmacokinetics of cefotaxime in
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58 El-Sayed MG Atef M and El-Komy AA (1994) Disposition kinetic of cephradine in
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59 Soback S and Ziv G (1988) Pharmacokinetics and bioavailability of ceftriaxone
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61 Abdulgafar O J Shaibu O B and Emmanuel U E (2011) Effect of Salmonella
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62 Ranjan R Birendra K R Amita R and Sanjeet K S (2011) Effect of Effect of E coli E
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63 Etuk EU and Onyeyili PA (2006) The effect of Salmonella infection on the plasma
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64 Wang E Bergeron Y and Bergeron MG (2005) Ceftriaxone pharmacokinetics in
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65 El-Sayed MG Hatem ME and El-Komy AA (1989) Disposition kinetic of
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66 Aramyona JJ Mora J Fraile LJ Garcia MA Abadia AR and Breganate MA
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57(4) 547-553
67 Rusmussen F (1966) Studies on the mammary excretion and absorbtion of drugs Vet
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constants of cefetamet cefotaxime and ceftriaxone the effect of the substituent at C3
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Statistical Analysis
The data were calculated as mean plusmn standard error All statistical analysis were carried out
according to[24]
using the scientific calculator CASIO fx 120
RESULTS
Following a single intravenous injection of 20 mg ceftriaxonekg bwt in normal goats
ceftriaxone could be detected therapeutically for 8 hours post intravenous injection The
serum concentration ndash time curve of ceftriaxone following intravenous injection showed that
the drug obeyed a two compartments open model (Figure 1) The disposition kinetics of
ceftriaxone following a single intravenous intramuscular injection were recorded in table (1)
Intramuscular injection of 20 mg ceftriaxone per kilogram body weight twice daily for five
consecutive days in normal and Salmonella typhimurium infected goats revealed a lower
significant serum ceftriaxone concentration after the first third fifth seventh ninth doses in
Salmonella typhimurium infected goats compared with normal goats The pharmacokinetic
parameters of ceftriaxone after repeated intramuscular injection in normal were compared to
those in Salmonella typhimurium infected goats (Table 2) and (Figure 2 amp 3)
The highest concentrations of ceftriaxone in milk were recorded 4 hours after each
intramuscular dose (Table 3) with a significant lower value in Salmonella typhimurium
infected goats compared with normal goats The calculated milkserum concentrations ratios
of ceftriaxone after repeated intramuscular injection (Table 4)
The amount of urine (mlmin) voided after repeated intramuscular injection of 20 mgkg bwt
Twice daily of ceftriaxone for five consecutive days in normal and experimentally
Salmonella typhimurium infected goats were recorded in table (5) The mean peak urine
concentrations of ceftriaxone (Table 6) were reached 2 hours after each intramuscular dose
with a lower significant concentration in Salmonella typhimurium infected goats compared
with normal goats Urineserum concentration ratios of ceftriaxone after repeated
intramuscular injection in normal and experimentally Salmonella typhimurium infected goats
were calculated and illustrated in table (7) Creatinine clearance (mlmin10 kg bwt)
expressing glomerular filtration rate from blood of goats was shown in table (8) The rate of
ceftriaxone clearance (mlmin10 kg bwt) from blood of goats was shown in table (9) The
ratio between ceftriaxone clearance and creatinine clearance was calculated and illustrated in
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
table (10) The data revealed a significant lower ratio in Salmonella typhimurium infected
goats compared with normal goats after the third fifth seventh ninth doses
Table (1) Pharmacokinetics parameters of ceftriaxone (μgml) following a single
intravenous and intramuscuer injection of 20 mgkg bwt in normal goats (n=4)
Intramusculer_
(XplusmnS E)
Intravenous_
(XplusmnS E) Unit Parameters
-------- 1213 plusmn321321 microgml Cdeg
4360plusmn12343 61390 plusmn330 microgml A
43440plusmn43660 636 plusmn43316 h-1
α
43433plusmn3340 43340 plusmn43442 H (α) 43 T
43420plusmn43233 4333plusmn131 h-1
K12
43446plusmn43400 43409plusmn231 h-1
K21
-------- 43440plusmn431 lkg Vdss
4321plusmn6340 43636plusmn1303 microgml B
434446plusmn43419 43443plusmn43136 h-1
β
43141plusmn39340 43411plusmn331 H t05(β))
4344plusmn43401 434440plusmn43409 lkgh Cl tot
-------- 1136plusmn2111300 microgmlh AUMC
-------- 43303 plusmn0314 H MRT
9300plusmn2439 30plusmn034330 microgmlh AUC
3392plusmn63329 -------- F
43436plusmn4361 -------- h-1
K01
43420plusmn3346 -------- h-1
T05(k01)
4342plusmn330 -------- H Tmax(calc))
43021plusmn04343 -------- μgml Cmax(calc)
Cdeg Drug concentration in the serum at zero time immediately after a single intravenous
injection (μgml) A amp B Zero time plasma drug concentration intercepts of biphasic
intravenous disposition curve The coefficient B is based on the terminal exponential phase
(μgml) α amp β Hybrid rate constant of biphasic intravenous disposition curve values of α
and β are related to the slopes of distribution and elimination phase respectively of
biexponential drug disposition curve (h-1
) T05 (α) Distribution half ndash life (h) t05 (β)
Elimination half ndash life (h) K12 First ndash order transfer rate constant for drug distribution from
Central to peripheral compartment (h-1
) K21 First order transfer rate constant for drug
distribution from Peripheral to central compartment (h-1
) Vdss The apparent volume of
distribution which was calculated by steady ndash state method (mlkg) AUMC Area under
moment curve MRT Mean residence time AUC Total area under the serum drug
concentration versus time curve from t = 0 to t = α after administration of a single dose F
Bioavailability Cmax maximum drug concentration Tmax time of maximum observed
concentration in blood
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Figure (1) Arthimatic plot of Serum concentrations of ceftriaxone (μgml) in normal
goats following a single intramuscular injection )diamsdiams( previously given the same doseby
a single intravenous injection () of 20 mg ceftriaxonekgbwt (n=4)
Figure (2) Semilogarthmic graph depicting the time course of ceftriaxone in serum of
normal goats following repeated ntramuscular injection of 20 mg ceftriaxonekgbwt
twice dialy for five consecutive days (n=4)
Figure (3) Semilogarthmic graph depicting the time course of ceftriaxone in serum of
experimentally Salmonella typhimurim infected goats following repeated ntramuscular
injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4) 3
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Table (2) Pharmacokinetic parameters of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected
goats following repeated ntramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)
Dose
Unit
عىهParameters
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1269plusmn0073 7409plusmn121 1352plusmn0132 6373plusmn147 1410plusmn0243 5923plusmn126 1461plusmn0214 5430plusmn125 1424plusmn0172 7635plusmn176 gmlmicro A
0651plusmn0049 plusmn000843116 0720plusmn0008 plusmn00413300 0823plusmn0006 plusmn00263322 0848plusmn0025 plusmn00233323 0786plusmn0028 133plusmn0033 h-1 Α
106plusmn0008 330plusmn0015 0962plusmn0011 0392plusmn0007 0841plusmn0007 0567plusmn012 0818plusmn0024 0569plusmn0012 0885plusmn0030 plusmn00124322 H T05(α)
248plusmn0019 168plusmn0047 203plusmn0075 181plusmn0033 267plusmn0039 120plusmn0028 248plusmn0060 122plusmn0026 222plusmn0100 136plusmn0027 h-1 Kab
0278plusmn0002 0412plusmn0009 0342plusmn0012 0383plusmn0008 0252plusmn0009 0567plusmn0011 0279plusmn0005 00569plusmn0011 0314plusmn0014 0 510plusmn0012 H T05(ab)
0627plusmn0008 0378plusmn0007 0430plusmn0008 0402plusmn0008 0113plusmn00027 0424plusmn0009 0117plusmn0004 0394plusmn0008 0116plusmn0003 0239plusmn0005 h-1 K12
121plusmn0013 0962plusmn0022 141plusmn0021 130plusmn0023 0666plusmn0019 0651plusmn0013 0683plusmn0020 0660plusmn0013 0761plusmn0039 0998plusmn0023 h-1 K21
115plusmn0035 129plusmn0026 104plusmn0047 112plusmn0024 106plusmn0037 122plusmn0025 110plusmn0077 119plusmn0023 0910plusmn0032 123plusmn0023 H Tmax
4182plusmn0628 6108plusmn140 3440plusmn0363 5135plusmn0860 3117plusmn0965 4774plusmn0854 2713plusmn0781 4243plusmn0 870 2479plusmn0547 4065plusmn0825 gmlmicro Cmax
4944plusmn0820 7195plusmn142 4199plusmn0702 6511plusmn130 3190plusmn0688 5117plusmn113 3185plusmn0909 4709plusmn0990 3256plusmn0918 6329plusmn139 gmlmicro B
0164plusmn0003 0189plusmn00043 0181plusmn0002 0178plusmn0004 0181plusmn00035 0167plusmn0004 0214plusmn0009 0195plusmn0005 0249plusmn0918 0272plusmn0006 h-1 β
423plusmn0079 367plusmn0086 381plusmn0047 388plusmn0089 382plusmn0074 415plusmn0081 325plusmn0139 355plusmn0075 277plusmn0056 255plusmn0050 H T05β
0879plusmn0015 0429plusmn0009 109plusmn0004 0426plusmn0009 133plusmn0022 0503plusmn0011 154plusmn0064 0675plusmn0013 171plusmn0060 0693plusmn0014 Lkgh Cltot
28358plusmn215 40775plusmn808 21784plusmn0888 34259plusmn720 17860plusmn155 30705plusmn601 15281plusmn239 24135plusmn555 12175plusmn144 20292plusmn487 gmlhmicro AUC
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (3) Milk concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats
following repeated ntramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)
Dose Time of
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
197plusmn0205 200plusmn0408 125plusmn0104 155plusmn0132 0887plusmn0013 0885plusmn014 0500plusmn0040 074plusmn0012 ------------ ------ Before
200plusmn0408 22plusmn0108 197plusmn0205 200plusmn0408 155plusmn0132 197plusmn0205 100plusmn000 155plusmn0132 ----------- -------- 050
526plusmn0166 700plusmn0408 300plusmn0408 64plusmn0163 25plusmn0204 600plusmn0408 155plusmn0132 582plusmn0118 100plusmn000 520plusmn0166 1
640plusmn0163 900plusmn0408 582plusmn0118 792plusmn0114 582plusmn0118 755plusmn0221 275plusmn0061 700plusmn0408 200plusmn0408 691plusmn0176 2
900plusmn0408 1512plusmn0125 640plusmn0163 1475plusmn0322 640plusmn0163 1400plusmn0408 600plusmn0408 1352plusmn0205 526plusmn166 1225plusmn0595 4
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350plusmn0353 400plusmn0408 300plusmn0408 392plusmn0125 300plusmn0408 35plusmn0353 275plusmn006 300plusmn0408 155plusmn0132 275plusmn0061 6
300 plusmn0408 35plusmn0353 125plusmn0104 200plusmn0408 125plusmn0104 155plusmn01 0825plusmn0062 100plusmn000 0500plusmn0040 0887plusmn0013 8
200plusmn0408 22plusmn0108 100plusmn000 155plusmn0132 100plusmn000 125plusmn0104 0730plusmn002 0825plusmn0078 0422plusmn000 073plusmn0020 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (4) Milkserum concentrations ratios of ceftriaxone in normal and experimentally Salmonella typhimurim infected
goats following repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice daily for five consecutive days (n=4)
Dose Time of
a
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
0400plusmn0049 025plusmn0063 0307plusmn0026 021plusmn0019 0365plusmn00064 016plusmn0026 0232plusmn0016 0205plusmn0002 -------- helliphelliphelliphellip Before
0057plusmn0125 0042plusmn00025 0062plusmn00062 0042plusmn0010 0575plusmn00062 0055plusmn0006 0067plusmn0016 0049plusmn0005 --------- -------- 050
0127plusmn00062 0115plusmn00064 008plusmn0012 0117plusmn0004 0088plusmn00054 0122plusmn0008 008plusmn0017 0126plusmn0028 0039plusmn0005 0122plusmn0004 1
018plusmn0008 0185plusmn0010 021plusmn0004 017plusmn0004 0182plusmn0054 0179plusmn0006 0112plusmn00025 0193plusmn0012 0097plusmn0020 019plusmn0004 2
0357plusmn0020 0425plusmn0005 033plusmn0021 045plusmn0009 0285plusmn0082 0494plusmn0015 0395plusmn0016 0572plusmn001 0415plusmn0017 054plusmn0027 4
018plusmn0015 016plusmn0016 0207plusmn0022 0175plusmn0006 0257plusmn0037 0180plusmn0017 0272plusmn0015 0201plusmn003 0196plusmn0016 0222plusmn0002 6
0212plusmn0033 0212plusmn0020 0200plusmn0044 0122plusmn0024 0152plusmn0011 014plusmn0022 0122plusmn00062 0102plusmn0001 0107plusmn00094 0117plusmn0002 8
0372plusmn0042 025plusmn001 0325plusmn0027 0192plusmn0014 0265plusmn00064 0185plusmn0015 0272plusmn0125 0195plusmn0012 0252plusmn0032 0275plusmn0009 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
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Table (5) The amount of urine (mlmin) voided in normal and experimentally Salmonella typhimurim infected goats following
repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)
Dose Time of a
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
plusmn00372344 126plusmn0034 130plusmn0030 130plusmn0028 118plusmn0066 118plusmn0067 108plusmn0013 108plusmn0008 ----------- -------- Before
0577plusmn0069 43494057plusmn 045plusmn0060 plusmn0064309 0312plusmn002 033plusmn0012 0340plusmn0024 033plusmn0012 0287plusmn0017 0272plusmn0014 050
0712plusmn0019 0692plusmn0014 068plusmn0081 0697plusmn0006 0672plusmn0011 0675plusmn 0009 0635plusmn0032 0655plusmn0010 0719plusmn0031 0697plusmn0015 1
0837plusmn0025 0787plusmn0021 0732plusmn0011 plusmn00054300 0715plusmn0011 0715plusmn002 0722plusmn0019 0702plusmn0018 0737plusmn0027 0762plusmn0041 2
0535plusmn0095 0507plusmn0021 0447plusmn0022 0452plusmn002 0402plusmn0075 0405plusmn0011 0400plusmn0057 0397plusmn0009 0380plusmn0004 038plusmn001 4
0437plusmn00094 0432plusmn0008 0400plusmn0010 0405plusmn0002 0380plusmn0007 plusmn00044319 0372plusmn0047 037plusmn 0007 0350plusmn0005 0365plusmn0006 6
0397plusmn0028 0410plusmn0008 0380plusmn0012 0395plusmn0009 0355plusmn0086 0352plusmn0007 0340plusmn0004 0345plusmn0005 0302plusmn0004 0335plusmn0005 8
0385plusmn001 0380plusmn0010 0385plusmn00064 0380plusmn0008 0365plusmn0064 0367plusmn0004 0362plusmn0086 0372plusmn0106 0327plusmn0006 0362plusmn0016 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (6) Urine concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats
following repeated intramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)
Dose Time of a
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1125plusmn150 1125plusmn15 735plusmn287 81plusmn324 183plusmn03 555plusmn798 37plusmn0811 1815plusmn43290 -------------- ------ Before
2415plusmn357 2625plusmn374 1695plusmn788 249plusmn574 10575plusmn64 2415plusmn357 5400plusmn273 2085plusmn991 102plusmn160 168plusmn547 050
26025plusmn787 2923plusmn479 22425plusmn1225 2805plusmn35 1695plusmn618 2705plusmn471 10200plusmn547 2415plusmn357 6975plusmn225 22425plusmn894 1
29295plusmn765 3012plusmn346 28575plusmn738 2964plusmn415 2355plusmn259 2923plusmn479 1635plusmn561 2645plusmn917 102plusmn547 24825plusmn616 2
23475plusmn430 2482plusmn616 23475plusmn1564 2415plusmn357 1695plusmn788 198plusmn848 8475plusmn309 1515plusmn708 60plusmn212 1185plusmn45 4
1905plusmn45 2355plusmn259 153plusmn519 1935plusmn960 114plusmn948 159plusmn173 6675plusmn309 1215plusmn45 1312plusmn0552 855plusmn193 6
153plusmn1024 1965plusmn135 1335plusmn1229 150plusmn34 735plusmn295 1365plusmn665 6181plusmn339 72plusmn244 907plusmn0951 5025plusmn143 8
135plusmn519 120plusmn346 11725plusmn1551 96plusmn874 525plusmn295 75plusmn173 153plusmn130 39plusmn212 3735plusmn0458 13125plusmn0552 12
Between normal and diseased
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Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (7) Urineserum concentrations ratios of ceftriaxone following repeated ntramuscular injection of 20 mg
ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats
(n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
229plusmn 163 1448plusmn0743 1885plusmn159 1125plusmn0484 533plusmn0260 1050plusmn358 175plusmn0380 4146plusmn116 ------- ------ Before
741plusmn0063 plusmn01553 58plusmn0242 plusmn0149390 422plusmn0206 683plusmn0106 245plusmn0092 667plusmn0306 0510plusmn0081 559plusmn0181 050
651plusmn0243 plusmn0065031 637plusmn0373 plusmn014431 565plusmn0243 plusmn0085300 360plusmn0303 plusmn0110312 279plusmn0121 534plusmn0248 1
836plusmn0150 plusmn00476322 862plusmn0180 plusmn010463 942plusmn0166 plusmn0130631 217plusmn0303 727plusmn0256 508plusmn0186 plusmn01680340 2
939plusmn0235 plusmn01580344 1006plusmn0710 plusmn00750310 999plusmn0542 plusmn02850344 565plusmn0223 641plusmn0241 48plusmn0164 plusmn014834 4
1005plusmn0418 2plusmn018813 1097plusmn0641 plusmn03979300 993plusmn0921 plusmn0252931 619plusmn0483 plusmn0362933 167plusmn0101 642plusmn0644 6
1091plusmn0649 plusmn075332339 1171plusmn0980 995plusmn0415 925plusmn0593 plusmn05593433 886plusmn0408 plusmn02510311 2055plusmn0311 plusmn02046310 8
2392plusmn129 plusmn032731396 1794plusmn0228 1222plusmn124 1418plusmn109 plusmn026733336 580plusmn0397 plusmn03951326 227plusmn0452 plusmn02740316 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (8) Creatinine clearance (mlmin10kgbwt) following repeated intramuscular injection of 20 mg ceftriaxonekgbwt
twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats (n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1115plusmn0703 2265plusmn167 481plusmn0409 672plusmn0817 669plusmn0672 1202plusmn0777 695plusmn0634 1724plusmn179 ----------- ------ Before
0703plusmn0091 147plusmn0305 0718plusmn0141 251plusmn0707 0547plusmn0055 0699plusmn0092 0802plusmn0099 103plusmn0106 295plusmn0124 0458plusmn0037 050
101plusmn0075 161plusmn0093 131plusmn0099 264plusmn0217 161plusmn0146 373plusmn0499 247plusmn0110 4755plusmn0582 214plusmn0234 103plusmn0166 1
157plusmn0198 387plusmn0340 173plusmn0501 267plusmn0217 187plusmn0563 287plusmn0499 451plusmn0223 972plusmn105 263plusmn0399 169plusmn0454 2
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184plusmn0095 346plusmn0444 173plusmn0501 436plusmn0599 383plusmn0299 682plusmn0584 328plusmn0253 119plusmn153 123plusmn0057 292plusmn0742 4
221plusmn0242 411plusmn0661 241plusmn0186 663plusmn0584 308plusmn0234 422plusmn0314 353plusmn0393 548plusmn0901 105plusmn0057 264plusmn0294 6
261plusmn0295 476plusmn0339 319plusmn0273 753plusmn0676 106plusmn0207 0773plusmn0049 228plusmn0175 456plusmn0340 206plusmn0160 404plusmn0419 8
310plusmn0218 409plusmn0434 3264plusmn0153 669plusmn0476 209plusmn0189 235plusmn0337 217plusmn0143 377plusmn0342 240plusmn0218 6055plusmn0176 12
Between normal and diseased
Plt 005 Plt001 Plt0001
Table (9) Ceftriaxone clearance (mlmin10kgbwt following repeated intramuscular injection of 20 mg ceftriaxone kgbwt
twice in normal and experimentally Salmonella typhimurim infected goats (n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1048plusmn121 0557plusmn684 895plusmn113 0547plusmn560 238plusmn0222 103plusmn 480 0668plusmn0157 0173plusmn216 -------- ----------- Before
156plusmn0251 43204plusmn3322 0936plusmn0162 43211plusmn3334 0473plusmn0037 43469plusmn43964 0300plusmn0028 43341plusmn080 0190plusmn0137 43400plusmn43642 050
166plusmn0079 43323plusmn3311 157plusmn0178 43419plusmn3301 137plusmn0115 43311plusmn33022 0883plusmn0054 43341plusmn 133 0616plusmn0153 43120plusmn3301 1
254plusmn0272 43361plusmn3391 222plusmn0093 4331plusmn3390 243plusmn0180 43209plusmn3309 183plusmn0149 43310plusmn2340 128plusmn0153 43312plusmn3390 2
181plusmn0136 43339plusmn3316 161plusmn0129 433plusmn3329 144plusmn0100 43412plusmn3349 0821plusmn0072 0063plusmn0977 0654plusmn0065 43400plusmn4306 4
160plusmn0177 43393plusmn336 152plusmn0200 43416plusmn331 135plusmn0118 4332plusmn3322 0897plusmn0052 43304plusmn3330 0212plusmn0022 43460plusmn43112 6
153plusmn0049 43291plusmn234 163plusmn0242 43346plusmn3300 0891plusmn0272 43306plusmn3310 108plusmn0071 43416plusmn04310 0229plusmn0046 43490plusmn43916 8
340plusmn0522 43214plusmn2341 249plusmn0150 43112plusmn3393 186plusmn0159 43320plusmn336 0773plusmn0094 43390plusmn 134 0264plusmn0043 43400plusmn 54369 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
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Table (10) Ceftriaxone clearancecreatinine clearance following repeated ntramuscular injection of 20 mg
ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats
(n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
0934plusmn0083 0305plusmn0013 183plusmn0116 0864plusmn0098 0358plusmn0018 0279plusmn0047 0099plusmn0020 0127plusmn0001 ------- ----------- Before
220plusmn0115 0819plusmn0044 131plusmn00414 0458plusmn0029 0876plusmn0063 126plusmn0068 0361plusmn0011 0813plusmn0031 0018plusmn0003 108plusmn0062 050
164plusmn0078 0818plusmn0029 118plusmn0068 0546plusmn0027 0858plusmn0052 0407plusmn0041 0331plusmn0009 0287plusmn0025 0324plusmn0011 0909plusmn0187 1
161plusmn0044 0488plusmn0005 232plusmn128 0329plusmn0027 169plusmn0464 0686plusmn0050 0409plusmn0020 0220plusmn0029 0512plusmn0077 266plusmn177 2
0933plusmn0024 0394plusmn0005 0948plusmn0062 0296plusmn0007 0381plusmn0027 0160plusmn0008 0235plusmn0014 0083plusmn0006 0528plusmn0028 0362plusmn0041 4
0726plusmn0018 0411plusmn0028 0639plusmn0066 0204plusmn0006 0446plusmn0034 0286plusmn0008 0238plusmn0019 0214plusmn0006 020plusmn0013 0382plusmn0028 6
0609plusmn0072 0425plusmn0036 0508plusmn0052 0192plusmn0009 0524plusmn0146 174plusmn0083 0477plusmn0015 0213plusmn00018 0109plusmn0185 0222plusmn0006 8
108plusmn0128 0496plusmn0012 0942plusmn0004 0265plusmn0030 0891plusmn0056 0706plusmn0103 0351plusmn0022 0354plusmn0018 0111plusmn0021 0098plusmn0018 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
DISCUSSION
In the present investigation intravenous injection of 20 mg ceftriaxonekgbwt in normal goats the drug showed high serum level
(92plusmn 0408 μgml) at 5 minutes post-injection then its concentration was decreased gradually till reached its minimum level (18
plusmn0816μgml) at 8hours post-injection
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In the present investigation the intravenous injection of 20 mg ceftriaxonekgbwt In normal
goats showed that the drug disposition best fitted a two-compartments- open model a
compartment of plasma and rapid equilibrating tissues and a deeper slower compartment
The obtained result is consistent with those reported for ceftriaxone in lactating goats[9]
lactating ewe[25]
domestic cat[15]
calves[26]
and patanwadi sheep[8]
Also this phenomenon is
in agreement with those reported for other cephalosporines as ceftazidime in a rabbit[27]
cefepime in dog and neonatal foals[28]
ewes[29]
ceftriaxone in goats[9]
cefipime in calves[30]
ceftiofur in cross-bred friesian cattle[31]
cefipime in calves[32]
ceftiofur in cows[33]
cefpirome
in cross-bred calves[3]
cefazidime in goats[35]
and cefquinome in sheep and goats[36]
cefipime
in chickens[37]
Ceftriaxone was distributed after intravenous injection with a distribution phase (α) equal to
656 per hour with a short distribution half ndash life [t05 (α)] equal to 0104 hour The shorter
distribution half-life of ceftriaxone in goats suggested the rapid distribution of the drug in
body tissue and fluid and that nearly similar to that recorded for ceftriaxone in lactating
goats(012 hour)[9]
for ceftriaxone in lactating ewes (0152 hour)[2]
and for ceftriaxone in
calves( 013hour)[26]
The rapid distribution of ceftriaxone in goats is supported by high rate constant of transfer of
the drug from central to peripheral compartment [K12 = 353 h-1
] as compared to the rate
constant of transfer of the drug from peripheral to central compartment [K21= 295 h-1
] This
value is nearly similar to those reported for cefotaxime in goats (K21=327 h-1
)[38]
On contrast
this value was higher than those recorded for ceftriaxone in lactating goats (K21=143 h-1
)[9]
in
lactating ewes (K21=125 h-1
)[25]
and in domestic cats (K21=154 h-1
)[15]
The apparent volume of distribution of ceftriaxone was (0355plusmn0004LKg) this value is
nearly similar to that recorded for cefaronide in sheep(039 LKg)[7]
cefotaxime in dog (048
lkg)[39]
in goat (051 lkg)
[40] for caphalexin in buffalo calves (041 Lkg)
[41] for cefipime in
ewes and calves (032 lkg) (043Lkg)[29]
and[30]
respectively For ceftriaxone in domestic
cats (057Lkg)[15]
in camel (032Lkg)[42]
On the other hand this result is differ than that
reported for cefotaxime in buffalo calves (117Lkg)[43]
High value of the volume of
distribution suggested extensive penetration power Drug with volume of distribution greater
than one literkilogram indicated wide distribution or extensive tissue binding or both[44]
The
apparent volume of distribution in the present study indicated moderate tissue penetrating
power This result agreed with[15]
for ceftriaxone in domestic cats
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Ceftriaxone is eliminated in the current study following a single intravenous injection with
elimination half ndashlife [t 05(β)] equal to 519 hours This observation is nearly agreed with the
data recorded for ceftizoxime in goats (624hours)[45]
On contrast this value was longer than
that reported for ceftriaxone in lactating ewe (175hours)[25]
for cefaronide in sheep (17
hours)[7]
For cephalexin in buffulo calves (216hours)[41]
for ceftriaxone in healthy horse
(162hours)[46]
also this value is longer than that recorded for ceftriaxone in lactating goats
(144hours)[9]
for cefipime in goats (186hours)[47]
The rate of total body clearance of ceftriaxone following a single intravenous injection is
0048 lkgh which equal to data reported for ceftizoxime in lactating goats (005Lkgh)[45]
On contrast this value is lower than that reported for ceftriaxone in buffulo calves lactating
goats buffulo calves (Bubalus bubalis) goats (capra hircus) patanwadi sheep (026 Lkgh)
(395 Lkgh) (440 Lkgh) (450 Lkgh) (391 Lkgh)[12913118]
respectively
The variation in total body clearance might be attributed to specific interspecies variation
handling of the drug method used healthy status of the animal[48]
The difference between values calculated for pharmacokinetic parameters may be attributed
to animal species the drug formulation employed the age the size or sex o l lf the animal
or even inter individual variation and also due to method of analysis of the drug[49]
Following a single intramuscular injection of 20 mg ceftriaxonekg bwt In normal goats the
drug reached its peak serum concentrations after one hour of injection with value
of(41μgml) Ceftriaxone could be detected in serum in a therapeutic level (263μgml) at 12
hours post-injection The reported peak serum concentrations neerly similar to that reported
for cephalexin in buffulo calves (457 microgml)[41]
These results is differed than those reported
for ceftriaxone in cross breed calves (188 microgml at 30 min[16]
in Kangro breed of goats
(Capra Hircus) (2640 microgml at 20 min[10][50]
found after intramuscular administration of
ceforazone peak plasma concentration was (976 microgml) at 45min This result was also higher
than that recorded for ceftriaxone in buffalo calves (158 microgml)[13]
The calculated maximum serum concentration (Cmax) is (40015 microgml) at maximum time
(tmax) of 157 hours The reported (Cmax) agreed with the data reported for cefipime in goats
(4932 microgml[47]
The reported maximum serum concentration (Cmax) is higher than that
reported for ceftriaxone in lactating goats(236 microgml)[9]
in lactating ewes (1722 microgml[25]
in
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
goats (2151 microgml)[11]
for cefquinome in camels (123 microgml)[51]
for ceftriaxone in calves
(1534 microgml)[26]
in patanwadi sheep (1553 microgml)[8]
for cefpirome in cattle (101 microgml)[52]
And for ceftiofur in chickens (2594 μgml)[37]
On the other hand the result was lower than
that reported by[6]
who observed the maximum serum concentration (Cmax) of ceftriaxone in
human after ntramuscular administration was (805 microgml) also it was lower than that
reported for ceftriaxone in dog (11510 microgml)[53]
in domestic cats (5440 microgml)[15]
and for
ceftazoxime in goats (8878 microgml)[45]
The reported [tmax] is neerly similar to that reported for ceftriaxone (104hours)in lactating
ewes by[25]
On contrast it is longer than those reported for ceftriaxone in dogs
(129hours)[53]
for ceftriaxone in lactating goats (07hours)[9]
also the result was longer than
that reported for ceftriaxone in domestic cats (033hours)[15]
in buffulo calves (05 hours)[13]
and for cefpirome in cattle (075hours)[52]
The reported [tmax] is shorter than those reported
for cefquinome in camels (425hours)[51]
in sheep and goats (261 and 262 hours)[36]
and for
ceftiofur in chickens (251 hours)[37]
The elimination half life [t05(β)]
following a single intramuscular administration was 1804 hours This value is nearly agreed
with that recorded for cefquinomein camels (1024hours)[52]
On contrast this result is longer
than that reported for cephalexin in buffalo calves (243hours)[41]
for ceftriaxone in lactating
ewes (177hours)[25]
in buffalo calves (438hours)[13]
in goats (203 hours)[11]
and for
cefipime in goats (165 hours)[47]
The rate of total body clearance of ceftriaxone following a single intramuscular injection is
0043lkgh This value was lower than that reported for ceftriaxone in buffulo calves
(401Lkgh)[13]
in goats (304 Lkgh)[11]
and in sheep (222 Lkgh)[8]
Bioavailability is the fraction of the drug administered by non vascular rout that gains
accesses to the systemic circulation The obtained result revealed that the calculated systemic
bioavailability percent was 6128 It is equal to that recorded for cefpirome in cow calves
(61)[54]
It is nearly equal to that recorded for ceftriaxone in sheep (64)[8]
On the other
hand this value is higher than those recorded for cefperazone in crossbred calves (481)[50]
for ceftriaxone in goats (59)[11]
in calves (47)[55]
On contrast this value is lower than
those reported for cefotaxime in two cats 982 and 93)[57]
for cephradine in goats
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
(739)[58]
for ceftazidime in a rabbit (966)[27]
for ceftriaxone in lactating goats (85)[9]
in lactating ewes (836)[25]
in domestic cats 8572[15]
for cefipime in goats 8645[47]
for ceftriaxone in buffulo calves 702[13]
and for ceftiofur in chickens 8890[37]
Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium
infected goats twics dialy for five days revealed that the drug could be detected in a
therapeutic level for 12hours following repeated intramuscular administrations and exceeded
the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]
The relative higher serum concentrations of ceftriaxone after the last dose compared to the
first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12
hours intervals for five consecutive days These observations agreed with data reported by[36]
on comparing the data of serum levels of repeated intramuscular injections with first
intramuscular injection it was revealed that repeated intramuscular injections of cefquinome
have cumulative effect in both species sheep and goats
The obtained result is inconsistent with that reported by[56]
who found thatwhen cefotaxime
was administered repetitively in patients the ratio of maximal serum levels after the last dose
to those after the first dose demonstrated minimal accumulation of intact drug and by[60]
who
found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in
buffalo calves
The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium
infected goats are significantly lower than those in normal goats following repeated
intramuscular injection These lower blood concentrations in Salmonella typhimurium
infected goats might be attributed to the higher penetrating power of ceftriaxone to the
diseased tissues[48]
This phenomenon is similar to data recorded by[61]
who suggested that
Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of
ceftriaxone These alterations might be due to fever and inflammation induced by
infections[59]
proved that the serum concentrations of cephradine following intramuscular
administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after
each intramuscular dose with a lower significant values recorded in Escherichia-coli infected
goats than in normal goatsAlso similer to that reported by[62]
who observed that the
maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
in comparison to normal sheepOn contrast[43]
reported that peak plasma level of cefotaxime
in febrile buffalo calves was higher than healthy buffalo calves
In this study the total body clearance (CLtot) in normal goats are significantly lower than in
Salmonella typhimurium infected goats This result supported by[61]
and[63]
fever and
inflammation are cardinal features in bacterial infection which may in turn caused an
increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all
these could lead to increased in the rate at which the drug was delivered to both organs which
were important sites of drug excretion This might somewhat explain the increase in the total
body clearance in infected goats This result is differ than that reported by[64]
who observed
that the clearance of ceftriaxone was significantly reduced in infected mice than in non
infected animals
The highest concentrations of ceftriaxone in milk are recorded 4 hours after each
intramuscular injection with a significant lower value in Salmonella typhimurium infected
goats than in normal goats This might be attributed to accumulation of drug in the inflammed
tissues[48]
This result is similar to those reported by[6559]
who found that milk concentrations
of gentamicin and cephradine were significantly lower in infected goats and cattle than in
normal ones respectively
The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the
non-ionic passive diffusion principle[66]
reported that most drug cross-lipid membranes by
passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly
influenced by the physicochemical properties of the drug[6768]
Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum
ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the
physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]
Milk
contains substantially more lipid and less protein than serum and is slightly more acidic
Therefore drugs which tend to concentrated in milk are weak bases with low serum protein
binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide
and aminothiazole also possesses an hydroxytriazinone group as new and additional
ionization center[70]
these compounds are sufficiently lipid- soluble to be able to penetrate
tissues
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
The dose of ceftriaxone used in the present study induced therapeutically concentrations in
milk These concentrations suggested that ceftriaxone would be efficacious in treatment of
mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily
for 3-5 days
The study showed that the urine concentrations of ceftriaxone are greater than the concurrent
serum concentrations following intramuscular injection This observation is similar to those
reported in cows after cephapirin administrations[71]
In the present study urine concentrations of ceftriaxone increased with the repetition of
dosing This observation supported by[72]
after repeated intramuscular administrations of
ceftriaxone in healthy volunteeres
The mean peak urine concentrations of ceftriaxone were reached 2 hours after each
intramuscular injection The lower urine ceftriaxone concentrations in Salmonella
typhimurium infected goats than in normal goats might be attributed to the accumulation of
the drug in the inflamed tissues[48]
The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower
ratio in Salmonella typhimurium infected goats than in normal goats at different time of
sampling This indicates that glomerular filteration seemed to be the main pathway of
ceftriaxone elimination This observation supported by[59]
who found that the ratio between
cephradine clearance from blood of goats to creatinine clearance showed a marked decrease
in Escherichia-coli infected goats than in normal goats This indicated that glomerular
filteration seemed to be the main pathway of cephradine elimination with a limited rate of
tubular reabsorption
CONCLUSION
The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value
referred a better absorption of ceftriaxone from its site of intramuscular administration The
high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular
administrations suggested that ceftriaxone could be used for treatment of mastitis caused by
Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats
The high concentrations of ceftriaxone in urine after repeated intramuscular administrations
suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in
goats
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42 Goudah A (2008) Pharmacokinetic parameters of ceftriaxone after single intravenous
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63 Etuk EU and Onyeyili PA (2006) The effect of Salmonella infection on the plasma
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64 Wang E Bergeron Y and Bergeron MG (2005) Ceftriaxone pharmacokinetics in
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65 El-Sayed MG Hatem ME and El-Komy AA (1989) Disposition kinetic of
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66 Aramyona JJ Mora J Fraile LJ Garcia MA Abadia AR and Breganate MA
(1996) Penetration of enrofloxacin and ciprofloxacin into breast milk and
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67 Rusmussen F (1966) Studies on the mammary excretion and absorbtion of drugs Vet
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70 Aleksić M Savić V Popović G Burić N and Kapetanović V (2005) Acidity
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71 Prades M Brown M P Gronwall R and Miles N S (1988) Pharmacokinetics of
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Ceftriaxone pharmacokinetics following multiple intramuscular dosing Euro J Clin
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
table (10) The data revealed a significant lower ratio in Salmonella typhimurium infected
goats compared with normal goats after the third fifth seventh ninth doses
Table (1) Pharmacokinetics parameters of ceftriaxone (μgml) following a single
intravenous and intramuscuer injection of 20 mgkg bwt in normal goats (n=4)
Intramusculer_
(XplusmnS E)
Intravenous_
(XplusmnS E) Unit Parameters
-------- 1213 plusmn321321 microgml Cdeg
4360plusmn12343 61390 plusmn330 microgml A
43440plusmn43660 636 plusmn43316 h-1
α
43433plusmn3340 43340 plusmn43442 H (α) 43 T
43420plusmn43233 4333plusmn131 h-1
K12
43446plusmn43400 43409plusmn231 h-1
K21
-------- 43440plusmn431 lkg Vdss
4321plusmn6340 43636plusmn1303 microgml B
434446plusmn43419 43443plusmn43136 h-1
β
43141plusmn39340 43411plusmn331 H t05(β))
4344plusmn43401 434440plusmn43409 lkgh Cl tot
-------- 1136plusmn2111300 microgmlh AUMC
-------- 43303 plusmn0314 H MRT
9300plusmn2439 30plusmn034330 microgmlh AUC
3392plusmn63329 -------- F
43436plusmn4361 -------- h-1
K01
43420plusmn3346 -------- h-1
T05(k01)
4342plusmn330 -------- H Tmax(calc))
43021plusmn04343 -------- μgml Cmax(calc)
Cdeg Drug concentration in the serum at zero time immediately after a single intravenous
injection (μgml) A amp B Zero time plasma drug concentration intercepts of biphasic
intravenous disposition curve The coefficient B is based on the terminal exponential phase
(μgml) α amp β Hybrid rate constant of biphasic intravenous disposition curve values of α
and β are related to the slopes of distribution and elimination phase respectively of
biexponential drug disposition curve (h-1
) T05 (α) Distribution half ndash life (h) t05 (β)
Elimination half ndash life (h) K12 First ndash order transfer rate constant for drug distribution from
Central to peripheral compartment (h-1
) K21 First order transfer rate constant for drug
distribution from Peripheral to central compartment (h-1
) Vdss The apparent volume of
distribution which was calculated by steady ndash state method (mlkg) AUMC Area under
moment curve MRT Mean residence time AUC Total area under the serum drug
concentration versus time curve from t = 0 to t = α after administration of a single dose F
Bioavailability Cmax maximum drug concentration Tmax time of maximum observed
concentration in blood
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
Figure (1) Arthimatic plot of Serum concentrations of ceftriaxone (μgml) in normal
goats following a single intramuscular injection )diamsdiams( previously given the same doseby
a single intravenous injection () of 20 mg ceftriaxonekgbwt (n=4)
Figure (2) Semilogarthmic graph depicting the time course of ceftriaxone in serum of
normal goats following repeated ntramuscular injection of 20 mg ceftriaxonekgbwt
twice dialy for five consecutive days (n=4)
Figure (3) Semilogarthmic graph depicting the time course of ceftriaxone in serum of
experimentally Salmonella typhimurim infected goats following repeated ntramuscular
injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4) 3
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
Table (2) Pharmacokinetic parameters of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected
goats following repeated ntramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)
Dose
Unit
عىهParameters
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1269plusmn0073 7409plusmn121 1352plusmn0132 6373plusmn147 1410plusmn0243 5923plusmn126 1461plusmn0214 5430plusmn125 1424plusmn0172 7635plusmn176 gmlmicro A
0651plusmn0049 plusmn000843116 0720plusmn0008 plusmn00413300 0823plusmn0006 plusmn00263322 0848plusmn0025 plusmn00233323 0786plusmn0028 133plusmn0033 h-1 Α
106plusmn0008 330plusmn0015 0962plusmn0011 0392plusmn0007 0841plusmn0007 0567plusmn012 0818plusmn0024 0569plusmn0012 0885plusmn0030 plusmn00124322 H T05(α)
248plusmn0019 168plusmn0047 203plusmn0075 181plusmn0033 267plusmn0039 120plusmn0028 248plusmn0060 122plusmn0026 222plusmn0100 136plusmn0027 h-1 Kab
0278plusmn0002 0412plusmn0009 0342plusmn0012 0383plusmn0008 0252plusmn0009 0567plusmn0011 0279plusmn0005 00569plusmn0011 0314plusmn0014 0 510plusmn0012 H T05(ab)
0627plusmn0008 0378plusmn0007 0430plusmn0008 0402plusmn0008 0113plusmn00027 0424plusmn0009 0117plusmn0004 0394plusmn0008 0116plusmn0003 0239plusmn0005 h-1 K12
121plusmn0013 0962plusmn0022 141plusmn0021 130plusmn0023 0666plusmn0019 0651plusmn0013 0683plusmn0020 0660plusmn0013 0761plusmn0039 0998plusmn0023 h-1 K21
115plusmn0035 129plusmn0026 104plusmn0047 112plusmn0024 106plusmn0037 122plusmn0025 110plusmn0077 119plusmn0023 0910plusmn0032 123plusmn0023 H Tmax
4182plusmn0628 6108plusmn140 3440plusmn0363 5135plusmn0860 3117plusmn0965 4774plusmn0854 2713plusmn0781 4243plusmn0 870 2479plusmn0547 4065plusmn0825 gmlmicro Cmax
4944plusmn0820 7195plusmn142 4199plusmn0702 6511plusmn130 3190plusmn0688 5117plusmn113 3185plusmn0909 4709plusmn0990 3256plusmn0918 6329plusmn139 gmlmicro B
0164plusmn0003 0189plusmn00043 0181plusmn0002 0178plusmn0004 0181plusmn00035 0167plusmn0004 0214plusmn0009 0195plusmn0005 0249plusmn0918 0272plusmn0006 h-1 β
423plusmn0079 367plusmn0086 381plusmn0047 388plusmn0089 382plusmn0074 415plusmn0081 325plusmn0139 355plusmn0075 277plusmn0056 255plusmn0050 H T05β
0879plusmn0015 0429plusmn0009 109plusmn0004 0426plusmn0009 133plusmn0022 0503plusmn0011 154plusmn0064 0675plusmn0013 171plusmn0060 0693plusmn0014 Lkgh Cltot
28358plusmn215 40775plusmn808 21784plusmn0888 34259plusmn720 17860plusmn155 30705plusmn601 15281plusmn239 24135plusmn555 12175plusmn144 20292plusmn487 gmlhmicro AUC
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (3) Milk concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats
following repeated ntramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)
Dose Time of
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
197plusmn0205 200plusmn0408 125plusmn0104 155plusmn0132 0887plusmn0013 0885plusmn014 0500plusmn0040 074plusmn0012 ------------ ------ Before
200plusmn0408 22plusmn0108 197plusmn0205 200plusmn0408 155plusmn0132 197plusmn0205 100plusmn000 155plusmn0132 ----------- -------- 050
526plusmn0166 700plusmn0408 300plusmn0408 64plusmn0163 25plusmn0204 600plusmn0408 155plusmn0132 582plusmn0118 100plusmn000 520plusmn0166 1
640plusmn0163 900plusmn0408 582plusmn0118 792plusmn0114 582plusmn0118 755plusmn0221 275plusmn0061 700plusmn0408 200plusmn0408 691plusmn0176 2
900plusmn0408 1512plusmn0125 640plusmn0163 1475plusmn0322 640plusmn0163 1400plusmn0408 600plusmn0408 1352plusmn0205 526plusmn166 1225plusmn0595 4
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350plusmn0353 400plusmn0408 300plusmn0408 392plusmn0125 300plusmn0408 35plusmn0353 275plusmn006 300plusmn0408 155plusmn0132 275plusmn0061 6
300 plusmn0408 35plusmn0353 125plusmn0104 200plusmn0408 125plusmn0104 155plusmn01 0825plusmn0062 100plusmn000 0500plusmn0040 0887plusmn0013 8
200plusmn0408 22plusmn0108 100plusmn000 155plusmn0132 100plusmn000 125plusmn0104 0730plusmn002 0825plusmn0078 0422plusmn000 073plusmn0020 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (4) Milkserum concentrations ratios of ceftriaxone in normal and experimentally Salmonella typhimurim infected
goats following repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice daily for five consecutive days (n=4)
Dose Time of
a
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
0400plusmn0049 025plusmn0063 0307plusmn0026 021plusmn0019 0365plusmn00064 016plusmn0026 0232plusmn0016 0205plusmn0002 -------- helliphelliphelliphellip Before
0057plusmn0125 0042plusmn00025 0062plusmn00062 0042plusmn0010 0575plusmn00062 0055plusmn0006 0067plusmn0016 0049plusmn0005 --------- -------- 050
0127plusmn00062 0115plusmn00064 008plusmn0012 0117plusmn0004 0088plusmn00054 0122plusmn0008 008plusmn0017 0126plusmn0028 0039plusmn0005 0122plusmn0004 1
018plusmn0008 0185plusmn0010 021plusmn0004 017plusmn0004 0182plusmn0054 0179plusmn0006 0112plusmn00025 0193plusmn0012 0097plusmn0020 019plusmn0004 2
0357plusmn0020 0425plusmn0005 033plusmn0021 045plusmn0009 0285plusmn0082 0494plusmn0015 0395plusmn0016 0572plusmn001 0415plusmn0017 054plusmn0027 4
018plusmn0015 016plusmn0016 0207plusmn0022 0175plusmn0006 0257plusmn0037 0180plusmn0017 0272plusmn0015 0201plusmn003 0196plusmn0016 0222plusmn0002 6
0212plusmn0033 0212plusmn0020 0200plusmn0044 0122plusmn0024 0152plusmn0011 014plusmn0022 0122plusmn00062 0102plusmn0001 0107plusmn00094 0117plusmn0002 8
0372plusmn0042 025plusmn001 0325plusmn0027 0192plusmn0014 0265plusmn00064 0185plusmn0015 0272plusmn0125 0195plusmn0012 0252plusmn0032 0275plusmn0009 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
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Table (5) The amount of urine (mlmin) voided in normal and experimentally Salmonella typhimurim infected goats following
repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)
Dose Time of a
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
plusmn00372344 126plusmn0034 130plusmn0030 130plusmn0028 118plusmn0066 118plusmn0067 108plusmn0013 108plusmn0008 ----------- -------- Before
0577plusmn0069 43494057plusmn 045plusmn0060 plusmn0064309 0312plusmn002 033plusmn0012 0340plusmn0024 033plusmn0012 0287plusmn0017 0272plusmn0014 050
0712plusmn0019 0692plusmn0014 068plusmn0081 0697plusmn0006 0672plusmn0011 0675plusmn 0009 0635plusmn0032 0655plusmn0010 0719plusmn0031 0697plusmn0015 1
0837plusmn0025 0787plusmn0021 0732plusmn0011 plusmn00054300 0715plusmn0011 0715plusmn002 0722plusmn0019 0702plusmn0018 0737plusmn0027 0762plusmn0041 2
0535plusmn0095 0507plusmn0021 0447plusmn0022 0452plusmn002 0402plusmn0075 0405plusmn0011 0400plusmn0057 0397plusmn0009 0380plusmn0004 038plusmn001 4
0437plusmn00094 0432plusmn0008 0400plusmn0010 0405plusmn0002 0380plusmn0007 plusmn00044319 0372plusmn0047 037plusmn 0007 0350plusmn0005 0365plusmn0006 6
0397plusmn0028 0410plusmn0008 0380plusmn0012 0395plusmn0009 0355plusmn0086 0352plusmn0007 0340plusmn0004 0345plusmn0005 0302plusmn0004 0335plusmn0005 8
0385plusmn001 0380plusmn0010 0385plusmn00064 0380plusmn0008 0365plusmn0064 0367plusmn0004 0362plusmn0086 0372plusmn0106 0327plusmn0006 0362plusmn0016 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (6) Urine concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats
following repeated intramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)
Dose Time of a
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1125plusmn150 1125plusmn15 735plusmn287 81plusmn324 183plusmn03 555plusmn798 37plusmn0811 1815plusmn43290 -------------- ------ Before
2415plusmn357 2625plusmn374 1695plusmn788 249plusmn574 10575plusmn64 2415plusmn357 5400plusmn273 2085plusmn991 102plusmn160 168plusmn547 050
26025plusmn787 2923plusmn479 22425plusmn1225 2805plusmn35 1695plusmn618 2705plusmn471 10200plusmn547 2415plusmn357 6975plusmn225 22425plusmn894 1
29295plusmn765 3012plusmn346 28575plusmn738 2964plusmn415 2355plusmn259 2923plusmn479 1635plusmn561 2645plusmn917 102plusmn547 24825plusmn616 2
23475plusmn430 2482plusmn616 23475plusmn1564 2415plusmn357 1695plusmn788 198plusmn848 8475plusmn309 1515plusmn708 60plusmn212 1185plusmn45 4
1905plusmn45 2355plusmn259 153plusmn519 1935plusmn960 114plusmn948 159plusmn173 6675plusmn309 1215plusmn45 1312plusmn0552 855plusmn193 6
153plusmn1024 1965plusmn135 1335plusmn1229 150plusmn34 735plusmn295 1365plusmn665 6181plusmn339 72plusmn244 907plusmn0951 5025plusmn143 8
135plusmn519 120plusmn346 11725plusmn1551 96plusmn874 525plusmn295 75plusmn173 153plusmn130 39plusmn212 3735plusmn0458 13125plusmn0552 12
Between normal and diseased
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Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (7) Urineserum concentrations ratios of ceftriaxone following repeated ntramuscular injection of 20 mg
ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats
(n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
229plusmn 163 1448plusmn0743 1885plusmn159 1125plusmn0484 533plusmn0260 1050plusmn358 175plusmn0380 4146plusmn116 ------- ------ Before
741plusmn0063 plusmn01553 58plusmn0242 plusmn0149390 422plusmn0206 683plusmn0106 245plusmn0092 667plusmn0306 0510plusmn0081 559plusmn0181 050
651plusmn0243 plusmn0065031 637plusmn0373 plusmn014431 565plusmn0243 plusmn0085300 360plusmn0303 plusmn0110312 279plusmn0121 534plusmn0248 1
836plusmn0150 plusmn00476322 862plusmn0180 plusmn010463 942plusmn0166 plusmn0130631 217plusmn0303 727plusmn0256 508plusmn0186 plusmn01680340 2
939plusmn0235 plusmn01580344 1006plusmn0710 plusmn00750310 999plusmn0542 plusmn02850344 565plusmn0223 641plusmn0241 48plusmn0164 plusmn014834 4
1005plusmn0418 2plusmn018813 1097plusmn0641 plusmn03979300 993plusmn0921 plusmn0252931 619plusmn0483 plusmn0362933 167plusmn0101 642plusmn0644 6
1091plusmn0649 plusmn075332339 1171plusmn0980 995plusmn0415 925plusmn0593 plusmn05593433 886plusmn0408 plusmn02510311 2055plusmn0311 plusmn02046310 8
2392plusmn129 plusmn032731396 1794plusmn0228 1222plusmn124 1418plusmn109 plusmn026733336 580plusmn0397 plusmn03951326 227plusmn0452 plusmn02740316 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (8) Creatinine clearance (mlmin10kgbwt) following repeated intramuscular injection of 20 mg ceftriaxonekgbwt
twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats (n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1115plusmn0703 2265plusmn167 481plusmn0409 672plusmn0817 669plusmn0672 1202plusmn0777 695plusmn0634 1724plusmn179 ----------- ------ Before
0703plusmn0091 147plusmn0305 0718plusmn0141 251plusmn0707 0547plusmn0055 0699plusmn0092 0802plusmn0099 103plusmn0106 295plusmn0124 0458plusmn0037 050
101plusmn0075 161plusmn0093 131plusmn0099 264plusmn0217 161plusmn0146 373plusmn0499 247plusmn0110 4755plusmn0582 214plusmn0234 103plusmn0166 1
157plusmn0198 387plusmn0340 173plusmn0501 267plusmn0217 187plusmn0563 287plusmn0499 451plusmn0223 972plusmn105 263plusmn0399 169plusmn0454 2
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
184plusmn0095 346plusmn0444 173plusmn0501 436plusmn0599 383plusmn0299 682plusmn0584 328plusmn0253 119plusmn153 123plusmn0057 292plusmn0742 4
221plusmn0242 411plusmn0661 241plusmn0186 663plusmn0584 308plusmn0234 422plusmn0314 353plusmn0393 548plusmn0901 105plusmn0057 264plusmn0294 6
261plusmn0295 476plusmn0339 319plusmn0273 753plusmn0676 106plusmn0207 0773plusmn0049 228plusmn0175 456plusmn0340 206plusmn0160 404plusmn0419 8
310plusmn0218 409plusmn0434 3264plusmn0153 669plusmn0476 209plusmn0189 235plusmn0337 217plusmn0143 377plusmn0342 240plusmn0218 6055plusmn0176 12
Between normal and diseased
Plt 005 Plt001 Plt0001
Table (9) Ceftriaxone clearance (mlmin10kgbwt following repeated intramuscular injection of 20 mg ceftriaxone kgbwt
twice in normal and experimentally Salmonella typhimurim infected goats (n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1048plusmn121 0557plusmn684 895plusmn113 0547plusmn560 238plusmn0222 103plusmn 480 0668plusmn0157 0173plusmn216 -------- ----------- Before
156plusmn0251 43204plusmn3322 0936plusmn0162 43211plusmn3334 0473plusmn0037 43469plusmn43964 0300plusmn0028 43341plusmn080 0190plusmn0137 43400plusmn43642 050
166plusmn0079 43323plusmn3311 157plusmn0178 43419plusmn3301 137plusmn0115 43311plusmn33022 0883plusmn0054 43341plusmn 133 0616plusmn0153 43120plusmn3301 1
254plusmn0272 43361plusmn3391 222plusmn0093 4331plusmn3390 243plusmn0180 43209plusmn3309 183plusmn0149 43310plusmn2340 128plusmn0153 43312plusmn3390 2
181plusmn0136 43339plusmn3316 161plusmn0129 433plusmn3329 144plusmn0100 43412plusmn3349 0821plusmn0072 0063plusmn0977 0654plusmn0065 43400plusmn4306 4
160plusmn0177 43393plusmn336 152plusmn0200 43416plusmn331 135plusmn0118 4332plusmn3322 0897plusmn0052 43304plusmn3330 0212plusmn0022 43460plusmn43112 6
153plusmn0049 43291plusmn234 163plusmn0242 43346plusmn3300 0891plusmn0272 43306plusmn3310 108plusmn0071 43416plusmn04310 0229plusmn0046 43490plusmn43916 8
340plusmn0522 43214plusmn2341 249plusmn0150 43112plusmn3393 186plusmn0159 43320plusmn336 0773plusmn0094 43390plusmn 134 0264plusmn0043 43400plusmn 54369 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
Table (10) Ceftriaxone clearancecreatinine clearance following repeated ntramuscular injection of 20 mg
ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats
(n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
0934plusmn0083 0305plusmn0013 183plusmn0116 0864plusmn0098 0358plusmn0018 0279plusmn0047 0099plusmn0020 0127plusmn0001 ------- ----------- Before
220plusmn0115 0819plusmn0044 131plusmn00414 0458plusmn0029 0876plusmn0063 126plusmn0068 0361plusmn0011 0813plusmn0031 0018plusmn0003 108plusmn0062 050
164plusmn0078 0818plusmn0029 118plusmn0068 0546plusmn0027 0858plusmn0052 0407plusmn0041 0331plusmn0009 0287plusmn0025 0324plusmn0011 0909plusmn0187 1
161plusmn0044 0488plusmn0005 232plusmn128 0329plusmn0027 169plusmn0464 0686plusmn0050 0409plusmn0020 0220plusmn0029 0512plusmn0077 266plusmn177 2
0933plusmn0024 0394plusmn0005 0948plusmn0062 0296plusmn0007 0381plusmn0027 0160plusmn0008 0235plusmn0014 0083plusmn0006 0528plusmn0028 0362plusmn0041 4
0726plusmn0018 0411plusmn0028 0639plusmn0066 0204plusmn0006 0446plusmn0034 0286plusmn0008 0238plusmn0019 0214plusmn0006 020plusmn0013 0382plusmn0028 6
0609plusmn0072 0425plusmn0036 0508plusmn0052 0192plusmn0009 0524plusmn0146 174plusmn0083 0477plusmn0015 0213plusmn00018 0109plusmn0185 0222plusmn0006 8
108plusmn0128 0496plusmn0012 0942plusmn0004 0265plusmn0030 0891plusmn0056 0706plusmn0103 0351plusmn0022 0354plusmn0018 0111plusmn0021 0098plusmn0018 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
DISCUSSION
In the present investigation intravenous injection of 20 mg ceftriaxonekgbwt in normal goats the drug showed high serum level
(92plusmn 0408 μgml) at 5 minutes post-injection then its concentration was decreased gradually till reached its minimum level (18
plusmn0816μgml) at 8hours post-injection
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In the present investigation the intravenous injection of 20 mg ceftriaxonekgbwt In normal
goats showed that the drug disposition best fitted a two-compartments- open model a
compartment of plasma and rapid equilibrating tissues and a deeper slower compartment
The obtained result is consistent with those reported for ceftriaxone in lactating goats[9]
lactating ewe[25]
domestic cat[15]
calves[26]
and patanwadi sheep[8]
Also this phenomenon is
in agreement with those reported for other cephalosporines as ceftazidime in a rabbit[27]
cefepime in dog and neonatal foals[28]
ewes[29]
ceftriaxone in goats[9]
cefipime in calves[30]
ceftiofur in cross-bred friesian cattle[31]
cefipime in calves[32]
ceftiofur in cows[33]
cefpirome
in cross-bred calves[3]
cefazidime in goats[35]
and cefquinome in sheep and goats[36]
cefipime
in chickens[37]
Ceftriaxone was distributed after intravenous injection with a distribution phase (α) equal to
656 per hour with a short distribution half ndash life [t05 (α)] equal to 0104 hour The shorter
distribution half-life of ceftriaxone in goats suggested the rapid distribution of the drug in
body tissue and fluid and that nearly similar to that recorded for ceftriaxone in lactating
goats(012 hour)[9]
for ceftriaxone in lactating ewes (0152 hour)[2]
and for ceftriaxone in
calves( 013hour)[26]
The rapid distribution of ceftriaxone in goats is supported by high rate constant of transfer of
the drug from central to peripheral compartment [K12 = 353 h-1
] as compared to the rate
constant of transfer of the drug from peripheral to central compartment [K21= 295 h-1
] This
value is nearly similar to those reported for cefotaxime in goats (K21=327 h-1
)[38]
On contrast
this value was higher than those recorded for ceftriaxone in lactating goats (K21=143 h-1
)[9]
in
lactating ewes (K21=125 h-1
)[25]
and in domestic cats (K21=154 h-1
)[15]
The apparent volume of distribution of ceftriaxone was (0355plusmn0004LKg) this value is
nearly similar to that recorded for cefaronide in sheep(039 LKg)[7]
cefotaxime in dog (048
lkg)[39]
in goat (051 lkg)
[40] for caphalexin in buffalo calves (041 Lkg)
[41] for cefipime in
ewes and calves (032 lkg) (043Lkg)[29]
and[30]
respectively For ceftriaxone in domestic
cats (057Lkg)[15]
in camel (032Lkg)[42]
On the other hand this result is differ than that
reported for cefotaxime in buffalo calves (117Lkg)[43]
High value of the volume of
distribution suggested extensive penetration power Drug with volume of distribution greater
than one literkilogram indicated wide distribution or extensive tissue binding or both[44]
The
apparent volume of distribution in the present study indicated moderate tissue penetrating
power This result agreed with[15]
for ceftriaxone in domestic cats
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Ceftriaxone is eliminated in the current study following a single intravenous injection with
elimination half ndashlife [t 05(β)] equal to 519 hours This observation is nearly agreed with the
data recorded for ceftizoxime in goats (624hours)[45]
On contrast this value was longer than
that reported for ceftriaxone in lactating ewe (175hours)[25]
for cefaronide in sheep (17
hours)[7]
For cephalexin in buffulo calves (216hours)[41]
for ceftriaxone in healthy horse
(162hours)[46]
also this value is longer than that recorded for ceftriaxone in lactating goats
(144hours)[9]
for cefipime in goats (186hours)[47]
The rate of total body clearance of ceftriaxone following a single intravenous injection is
0048 lkgh which equal to data reported for ceftizoxime in lactating goats (005Lkgh)[45]
On contrast this value is lower than that reported for ceftriaxone in buffulo calves lactating
goats buffulo calves (Bubalus bubalis) goats (capra hircus) patanwadi sheep (026 Lkgh)
(395 Lkgh) (440 Lkgh) (450 Lkgh) (391 Lkgh)[12913118]
respectively
The variation in total body clearance might be attributed to specific interspecies variation
handling of the drug method used healthy status of the animal[48]
The difference between values calculated for pharmacokinetic parameters may be attributed
to animal species the drug formulation employed the age the size or sex o l lf the animal
or even inter individual variation and also due to method of analysis of the drug[49]
Following a single intramuscular injection of 20 mg ceftriaxonekg bwt In normal goats the
drug reached its peak serum concentrations after one hour of injection with value
of(41μgml) Ceftriaxone could be detected in serum in a therapeutic level (263μgml) at 12
hours post-injection The reported peak serum concentrations neerly similar to that reported
for cephalexin in buffulo calves (457 microgml)[41]
These results is differed than those reported
for ceftriaxone in cross breed calves (188 microgml at 30 min[16]
in Kangro breed of goats
(Capra Hircus) (2640 microgml at 20 min[10][50]
found after intramuscular administration of
ceforazone peak plasma concentration was (976 microgml) at 45min This result was also higher
than that recorded for ceftriaxone in buffalo calves (158 microgml)[13]
The calculated maximum serum concentration (Cmax) is (40015 microgml) at maximum time
(tmax) of 157 hours The reported (Cmax) agreed with the data reported for cefipime in goats
(4932 microgml[47]
The reported maximum serum concentration (Cmax) is higher than that
reported for ceftriaxone in lactating goats(236 microgml)[9]
in lactating ewes (1722 microgml[25]
in
wwwwjppscom Vol 5 Issue 01 2016
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
goats (2151 microgml)[11]
for cefquinome in camels (123 microgml)[51]
for ceftriaxone in calves
(1534 microgml)[26]
in patanwadi sheep (1553 microgml)[8]
for cefpirome in cattle (101 microgml)[52]
And for ceftiofur in chickens (2594 μgml)[37]
On the other hand the result was lower than
that reported by[6]
who observed the maximum serum concentration (Cmax) of ceftriaxone in
human after ntramuscular administration was (805 microgml) also it was lower than that
reported for ceftriaxone in dog (11510 microgml)[53]
in domestic cats (5440 microgml)[15]
and for
ceftazoxime in goats (8878 microgml)[45]
The reported [tmax] is neerly similar to that reported for ceftriaxone (104hours)in lactating
ewes by[25]
On contrast it is longer than those reported for ceftriaxone in dogs
(129hours)[53]
for ceftriaxone in lactating goats (07hours)[9]
also the result was longer than
that reported for ceftriaxone in domestic cats (033hours)[15]
in buffulo calves (05 hours)[13]
and for cefpirome in cattle (075hours)[52]
The reported [tmax] is shorter than those reported
for cefquinome in camels (425hours)[51]
in sheep and goats (261 and 262 hours)[36]
and for
ceftiofur in chickens (251 hours)[37]
The elimination half life [t05(β)]
following a single intramuscular administration was 1804 hours This value is nearly agreed
with that recorded for cefquinomein camels (1024hours)[52]
On contrast this result is longer
than that reported for cephalexin in buffalo calves (243hours)[41]
for ceftriaxone in lactating
ewes (177hours)[25]
in buffalo calves (438hours)[13]
in goats (203 hours)[11]
and for
cefipime in goats (165 hours)[47]
The rate of total body clearance of ceftriaxone following a single intramuscular injection is
0043lkgh This value was lower than that reported for ceftriaxone in buffulo calves
(401Lkgh)[13]
in goats (304 Lkgh)[11]
and in sheep (222 Lkgh)[8]
Bioavailability is the fraction of the drug administered by non vascular rout that gains
accesses to the systemic circulation The obtained result revealed that the calculated systemic
bioavailability percent was 6128 It is equal to that recorded for cefpirome in cow calves
(61)[54]
It is nearly equal to that recorded for ceftriaxone in sheep (64)[8]
On the other
hand this value is higher than those recorded for cefperazone in crossbred calves (481)[50]
for ceftriaxone in goats (59)[11]
in calves (47)[55]
On contrast this value is lower than
those reported for cefotaxime in two cats 982 and 93)[57]
for cephradine in goats
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
(739)[58]
for ceftazidime in a rabbit (966)[27]
for ceftriaxone in lactating goats (85)[9]
in lactating ewes (836)[25]
in domestic cats 8572[15]
for cefipime in goats 8645[47]
for ceftriaxone in buffulo calves 702[13]
and for ceftiofur in chickens 8890[37]
Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium
infected goats twics dialy for five days revealed that the drug could be detected in a
therapeutic level for 12hours following repeated intramuscular administrations and exceeded
the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]
The relative higher serum concentrations of ceftriaxone after the last dose compared to the
first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12
hours intervals for five consecutive days These observations agreed with data reported by[36]
on comparing the data of serum levels of repeated intramuscular injections with first
intramuscular injection it was revealed that repeated intramuscular injections of cefquinome
have cumulative effect in both species sheep and goats
The obtained result is inconsistent with that reported by[56]
who found thatwhen cefotaxime
was administered repetitively in patients the ratio of maximal serum levels after the last dose
to those after the first dose demonstrated minimal accumulation of intact drug and by[60]
who
found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in
buffalo calves
The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium
infected goats are significantly lower than those in normal goats following repeated
intramuscular injection These lower blood concentrations in Salmonella typhimurium
infected goats might be attributed to the higher penetrating power of ceftriaxone to the
diseased tissues[48]
This phenomenon is similar to data recorded by[61]
who suggested that
Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of
ceftriaxone These alterations might be due to fever and inflammation induced by
infections[59]
proved that the serum concentrations of cephradine following intramuscular
administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after
each intramuscular dose with a lower significant values recorded in Escherichia-coli infected
goats than in normal goatsAlso similer to that reported by[62]
who observed that the
maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
in comparison to normal sheepOn contrast[43]
reported that peak plasma level of cefotaxime
in febrile buffalo calves was higher than healthy buffalo calves
In this study the total body clearance (CLtot) in normal goats are significantly lower than in
Salmonella typhimurium infected goats This result supported by[61]
and[63]
fever and
inflammation are cardinal features in bacterial infection which may in turn caused an
increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all
these could lead to increased in the rate at which the drug was delivered to both organs which
were important sites of drug excretion This might somewhat explain the increase in the total
body clearance in infected goats This result is differ than that reported by[64]
who observed
that the clearance of ceftriaxone was significantly reduced in infected mice than in non
infected animals
The highest concentrations of ceftriaxone in milk are recorded 4 hours after each
intramuscular injection with a significant lower value in Salmonella typhimurium infected
goats than in normal goats This might be attributed to accumulation of drug in the inflammed
tissues[48]
This result is similar to those reported by[6559]
who found that milk concentrations
of gentamicin and cephradine were significantly lower in infected goats and cattle than in
normal ones respectively
The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the
non-ionic passive diffusion principle[66]
reported that most drug cross-lipid membranes by
passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly
influenced by the physicochemical properties of the drug[6768]
Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum
ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the
physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]
Milk
contains substantially more lipid and less protein than serum and is slightly more acidic
Therefore drugs which tend to concentrated in milk are weak bases with low serum protein
binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide
and aminothiazole also possesses an hydroxytriazinone group as new and additional
ionization center[70]
these compounds are sufficiently lipid- soluble to be able to penetrate
tissues
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
The dose of ceftriaxone used in the present study induced therapeutically concentrations in
milk These concentrations suggested that ceftriaxone would be efficacious in treatment of
mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily
for 3-5 days
The study showed that the urine concentrations of ceftriaxone are greater than the concurrent
serum concentrations following intramuscular injection This observation is similar to those
reported in cows after cephapirin administrations[71]
In the present study urine concentrations of ceftriaxone increased with the repetition of
dosing This observation supported by[72]
after repeated intramuscular administrations of
ceftriaxone in healthy volunteeres
The mean peak urine concentrations of ceftriaxone were reached 2 hours after each
intramuscular injection The lower urine ceftriaxone concentrations in Salmonella
typhimurium infected goats than in normal goats might be attributed to the accumulation of
the drug in the inflamed tissues[48]
The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower
ratio in Salmonella typhimurium infected goats than in normal goats at different time of
sampling This indicates that glomerular filteration seemed to be the main pathway of
ceftriaxone elimination This observation supported by[59]
who found that the ratio between
cephradine clearance from blood of goats to creatinine clearance showed a marked decrease
in Escherichia-coli infected goats than in normal goats This indicated that glomerular
filteration seemed to be the main pathway of cephradine elimination with a limited rate of
tubular reabsorption
CONCLUSION
The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value
referred a better absorption of ceftriaxone from its site of intramuscular administration The
high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular
administrations suggested that ceftriaxone could be used for treatment of mastitis caused by
Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats
The high concentrations of ceftriaxone in urine after repeated intramuscular administrations
suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in
goats
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Pharmacokinetics of cefotaxime and its metabolites in subjects with normal and impaired
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58 El-Sayed MG Atef M and El-Komy AA (1994) Disposition kinetic of cephradine in
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65 El-Sayed MG Hatem ME and El-Komy AA (1989) Disposition kinetic of
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66 Aramyona JJ Mora J Fraile LJ Garcia MA Abadia AR and Breganate MA
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
Figure (1) Arthimatic plot of Serum concentrations of ceftriaxone (μgml) in normal
goats following a single intramuscular injection )diamsdiams( previously given the same doseby
a single intravenous injection () of 20 mg ceftriaxonekgbwt (n=4)
Figure (2) Semilogarthmic graph depicting the time course of ceftriaxone in serum of
normal goats following repeated ntramuscular injection of 20 mg ceftriaxonekgbwt
twice dialy for five consecutive days (n=4)
Figure (3) Semilogarthmic graph depicting the time course of ceftriaxone in serum of
experimentally Salmonella typhimurim infected goats following repeated ntramuscular
injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4) 3
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Table (2) Pharmacokinetic parameters of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected
goats following repeated ntramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)
Dose
Unit
عىهParameters
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1269plusmn0073 7409plusmn121 1352plusmn0132 6373plusmn147 1410plusmn0243 5923plusmn126 1461plusmn0214 5430plusmn125 1424plusmn0172 7635plusmn176 gmlmicro A
0651plusmn0049 plusmn000843116 0720plusmn0008 plusmn00413300 0823plusmn0006 plusmn00263322 0848plusmn0025 plusmn00233323 0786plusmn0028 133plusmn0033 h-1 Α
106plusmn0008 330plusmn0015 0962plusmn0011 0392plusmn0007 0841plusmn0007 0567plusmn012 0818plusmn0024 0569plusmn0012 0885plusmn0030 plusmn00124322 H T05(α)
248plusmn0019 168plusmn0047 203plusmn0075 181plusmn0033 267plusmn0039 120plusmn0028 248plusmn0060 122plusmn0026 222plusmn0100 136plusmn0027 h-1 Kab
0278plusmn0002 0412plusmn0009 0342plusmn0012 0383plusmn0008 0252plusmn0009 0567plusmn0011 0279plusmn0005 00569plusmn0011 0314plusmn0014 0 510plusmn0012 H T05(ab)
0627plusmn0008 0378plusmn0007 0430plusmn0008 0402plusmn0008 0113plusmn00027 0424plusmn0009 0117plusmn0004 0394plusmn0008 0116plusmn0003 0239plusmn0005 h-1 K12
121plusmn0013 0962plusmn0022 141plusmn0021 130plusmn0023 0666plusmn0019 0651plusmn0013 0683plusmn0020 0660plusmn0013 0761plusmn0039 0998plusmn0023 h-1 K21
115plusmn0035 129plusmn0026 104plusmn0047 112plusmn0024 106plusmn0037 122plusmn0025 110plusmn0077 119plusmn0023 0910plusmn0032 123plusmn0023 H Tmax
4182plusmn0628 6108plusmn140 3440plusmn0363 5135plusmn0860 3117plusmn0965 4774plusmn0854 2713plusmn0781 4243plusmn0 870 2479plusmn0547 4065plusmn0825 gmlmicro Cmax
4944plusmn0820 7195plusmn142 4199plusmn0702 6511plusmn130 3190plusmn0688 5117plusmn113 3185plusmn0909 4709plusmn0990 3256plusmn0918 6329plusmn139 gmlmicro B
0164plusmn0003 0189plusmn00043 0181plusmn0002 0178plusmn0004 0181plusmn00035 0167plusmn0004 0214plusmn0009 0195plusmn0005 0249plusmn0918 0272plusmn0006 h-1 β
423plusmn0079 367plusmn0086 381plusmn0047 388plusmn0089 382plusmn0074 415plusmn0081 325plusmn0139 355plusmn0075 277plusmn0056 255plusmn0050 H T05β
0879plusmn0015 0429plusmn0009 109plusmn0004 0426plusmn0009 133plusmn0022 0503plusmn0011 154plusmn0064 0675plusmn0013 171plusmn0060 0693plusmn0014 Lkgh Cltot
28358plusmn215 40775plusmn808 21784plusmn0888 34259plusmn720 17860plusmn155 30705plusmn601 15281plusmn239 24135plusmn555 12175plusmn144 20292plusmn487 gmlhmicro AUC
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (3) Milk concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats
following repeated ntramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)
Dose Time of
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
197plusmn0205 200plusmn0408 125plusmn0104 155plusmn0132 0887plusmn0013 0885plusmn014 0500plusmn0040 074plusmn0012 ------------ ------ Before
200plusmn0408 22plusmn0108 197plusmn0205 200plusmn0408 155plusmn0132 197plusmn0205 100plusmn000 155plusmn0132 ----------- -------- 050
526plusmn0166 700plusmn0408 300plusmn0408 64plusmn0163 25plusmn0204 600plusmn0408 155plusmn0132 582plusmn0118 100plusmn000 520plusmn0166 1
640plusmn0163 900plusmn0408 582plusmn0118 792plusmn0114 582plusmn0118 755plusmn0221 275plusmn0061 700plusmn0408 200plusmn0408 691plusmn0176 2
900plusmn0408 1512plusmn0125 640plusmn0163 1475plusmn0322 640plusmn0163 1400plusmn0408 600plusmn0408 1352plusmn0205 526plusmn166 1225plusmn0595 4
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350plusmn0353 400plusmn0408 300plusmn0408 392plusmn0125 300plusmn0408 35plusmn0353 275plusmn006 300plusmn0408 155plusmn0132 275plusmn0061 6
300 plusmn0408 35plusmn0353 125plusmn0104 200plusmn0408 125plusmn0104 155plusmn01 0825plusmn0062 100plusmn000 0500plusmn0040 0887plusmn0013 8
200plusmn0408 22plusmn0108 100plusmn000 155plusmn0132 100plusmn000 125plusmn0104 0730plusmn002 0825plusmn0078 0422plusmn000 073plusmn0020 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (4) Milkserum concentrations ratios of ceftriaxone in normal and experimentally Salmonella typhimurim infected
goats following repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice daily for five consecutive days (n=4)
Dose Time of
a
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
0400plusmn0049 025plusmn0063 0307plusmn0026 021plusmn0019 0365plusmn00064 016plusmn0026 0232plusmn0016 0205plusmn0002 -------- helliphelliphelliphellip Before
0057plusmn0125 0042plusmn00025 0062plusmn00062 0042plusmn0010 0575plusmn00062 0055plusmn0006 0067plusmn0016 0049plusmn0005 --------- -------- 050
0127plusmn00062 0115plusmn00064 008plusmn0012 0117plusmn0004 0088plusmn00054 0122plusmn0008 008plusmn0017 0126plusmn0028 0039plusmn0005 0122plusmn0004 1
018plusmn0008 0185plusmn0010 021plusmn0004 017plusmn0004 0182plusmn0054 0179plusmn0006 0112plusmn00025 0193plusmn0012 0097plusmn0020 019plusmn0004 2
0357plusmn0020 0425plusmn0005 033plusmn0021 045plusmn0009 0285plusmn0082 0494plusmn0015 0395plusmn0016 0572plusmn001 0415plusmn0017 054plusmn0027 4
018plusmn0015 016plusmn0016 0207plusmn0022 0175plusmn0006 0257plusmn0037 0180plusmn0017 0272plusmn0015 0201plusmn003 0196plusmn0016 0222plusmn0002 6
0212plusmn0033 0212plusmn0020 0200plusmn0044 0122plusmn0024 0152plusmn0011 014plusmn0022 0122plusmn00062 0102plusmn0001 0107plusmn00094 0117plusmn0002 8
0372plusmn0042 025plusmn001 0325plusmn0027 0192plusmn0014 0265plusmn00064 0185plusmn0015 0272plusmn0125 0195plusmn0012 0252plusmn0032 0275plusmn0009 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
Table (5) The amount of urine (mlmin) voided in normal and experimentally Salmonella typhimurim infected goats following
repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)
Dose Time of a
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
plusmn00372344 126plusmn0034 130plusmn0030 130plusmn0028 118plusmn0066 118plusmn0067 108plusmn0013 108plusmn0008 ----------- -------- Before
0577plusmn0069 43494057plusmn 045plusmn0060 plusmn0064309 0312plusmn002 033plusmn0012 0340plusmn0024 033plusmn0012 0287plusmn0017 0272plusmn0014 050
0712plusmn0019 0692plusmn0014 068plusmn0081 0697plusmn0006 0672plusmn0011 0675plusmn 0009 0635plusmn0032 0655plusmn0010 0719plusmn0031 0697plusmn0015 1
0837plusmn0025 0787plusmn0021 0732plusmn0011 plusmn00054300 0715plusmn0011 0715plusmn002 0722plusmn0019 0702plusmn0018 0737plusmn0027 0762plusmn0041 2
0535plusmn0095 0507plusmn0021 0447plusmn0022 0452plusmn002 0402plusmn0075 0405plusmn0011 0400plusmn0057 0397plusmn0009 0380plusmn0004 038plusmn001 4
0437plusmn00094 0432plusmn0008 0400plusmn0010 0405plusmn0002 0380plusmn0007 plusmn00044319 0372plusmn0047 037plusmn 0007 0350plusmn0005 0365plusmn0006 6
0397plusmn0028 0410plusmn0008 0380plusmn0012 0395plusmn0009 0355plusmn0086 0352plusmn0007 0340plusmn0004 0345plusmn0005 0302plusmn0004 0335plusmn0005 8
0385plusmn001 0380plusmn0010 0385plusmn00064 0380plusmn0008 0365plusmn0064 0367plusmn0004 0362plusmn0086 0372plusmn0106 0327plusmn0006 0362plusmn0016 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (6) Urine concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats
following repeated intramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)
Dose Time of a
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1125plusmn150 1125plusmn15 735plusmn287 81plusmn324 183plusmn03 555plusmn798 37plusmn0811 1815plusmn43290 -------------- ------ Before
2415plusmn357 2625plusmn374 1695plusmn788 249plusmn574 10575plusmn64 2415plusmn357 5400plusmn273 2085plusmn991 102plusmn160 168plusmn547 050
26025plusmn787 2923plusmn479 22425plusmn1225 2805plusmn35 1695plusmn618 2705plusmn471 10200plusmn547 2415plusmn357 6975plusmn225 22425plusmn894 1
29295plusmn765 3012plusmn346 28575plusmn738 2964plusmn415 2355plusmn259 2923plusmn479 1635plusmn561 2645plusmn917 102plusmn547 24825plusmn616 2
23475plusmn430 2482plusmn616 23475plusmn1564 2415plusmn357 1695plusmn788 198plusmn848 8475plusmn309 1515plusmn708 60plusmn212 1185plusmn45 4
1905plusmn45 2355plusmn259 153plusmn519 1935plusmn960 114plusmn948 159plusmn173 6675plusmn309 1215plusmn45 1312plusmn0552 855plusmn193 6
153plusmn1024 1965plusmn135 1335plusmn1229 150plusmn34 735plusmn295 1365plusmn665 6181plusmn339 72plusmn244 907plusmn0951 5025plusmn143 8
135plusmn519 120plusmn346 11725plusmn1551 96plusmn874 525plusmn295 75plusmn173 153plusmn130 39plusmn212 3735plusmn0458 13125plusmn0552 12
Between normal and diseased
wwwwjppscom Vol 5 Issue 02 2016
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (7) Urineserum concentrations ratios of ceftriaxone following repeated ntramuscular injection of 20 mg
ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats
(n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
229plusmn 163 1448plusmn0743 1885plusmn159 1125plusmn0484 533plusmn0260 1050plusmn358 175plusmn0380 4146plusmn116 ------- ------ Before
741plusmn0063 plusmn01553 58plusmn0242 plusmn0149390 422plusmn0206 683plusmn0106 245plusmn0092 667plusmn0306 0510plusmn0081 559plusmn0181 050
651plusmn0243 plusmn0065031 637plusmn0373 plusmn014431 565plusmn0243 plusmn0085300 360plusmn0303 plusmn0110312 279plusmn0121 534plusmn0248 1
836plusmn0150 plusmn00476322 862plusmn0180 plusmn010463 942plusmn0166 plusmn0130631 217plusmn0303 727plusmn0256 508plusmn0186 plusmn01680340 2
939plusmn0235 plusmn01580344 1006plusmn0710 plusmn00750310 999plusmn0542 plusmn02850344 565plusmn0223 641plusmn0241 48plusmn0164 plusmn014834 4
1005plusmn0418 2plusmn018813 1097plusmn0641 plusmn03979300 993plusmn0921 plusmn0252931 619plusmn0483 plusmn0362933 167plusmn0101 642plusmn0644 6
1091plusmn0649 plusmn075332339 1171plusmn0980 995plusmn0415 925plusmn0593 plusmn05593433 886plusmn0408 plusmn02510311 2055plusmn0311 plusmn02046310 8
2392plusmn129 plusmn032731396 1794plusmn0228 1222plusmn124 1418plusmn109 plusmn026733336 580plusmn0397 plusmn03951326 227plusmn0452 plusmn02740316 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (8) Creatinine clearance (mlmin10kgbwt) following repeated intramuscular injection of 20 mg ceftriaxonekgbwt
twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats (n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1115plusmn0703 2265plusmn167 481plusmn0409 672plusmn0817 669plusmn0672 1202plusmn0777 695plusmn0634 1724plusmn179 ----------- ------ Before
0703plusmn0091 147plusmn0305 0718plusmn0141 251plusmn0707 0547plusmn0055 0699plusmn0092 0802plusmn0099 103plusmn0106 295plusmn0124 0458plusmn0037 050
101plusmn0075 161plusmn0093 131plusmn0099 264plusmn0217 161plusmn0146 373plusmn0499 247plusmn0110 4755plusmn0582 214plusmn0234 103plusmn0166 1
157plusmn0198 387plusmn0340 173plusmn0501 267plusmn0217 187plusmn0563 287plusmn0499 451plusmn0223 972plusmn105 263plusmn0399 169plusmn0454 2
wwwwjppscom Vol 5 Issue 02 2016
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
184plusmn0095 346plusmn0444 173plusmn0501 436plusmn0599 383plusmn0299 682plusmn0584 328plusmn0253 119plusmn153 123plusmn0057 292plusmn0742 4
221plusmn0242 411plusmn0661 241plusmn0186 663plusmn0584 308plusmn0234 422plusmn0314 353plusmn0393 548plusmn0901 105plusmn0057 264plusmn0294 6
261plusmn0295 476plusmn0339 319plusmn0273 753plusmn0676 106plusmn0207 0773plusmn0049 228plusmn0175 456plusmn0340 206plusmn0160 404plusmn0419 8
310plusmn0218 409plusmn0434 3264plusmn0153 669plusmn0476 209plusmn0189 235plusmn0337 217plusmn0143 377plusmn0342 240plusmn0218 6055plusmn0176 12
Between normal and diseased
Plt 005 Plt001 Plt0001
Table (9) Ceftriaxone clearance (mlmin10kgbwt following repeated intramuscular injection of 20 mg ceftriaxone kgbwt
twice in normal and experimentally Salmonella typhimurim infected goats (n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1048plusmn121 0557plusmn684 895plusmn113 0547plusmn560 238plusmn0222 103plusmn 480 0668plusmn0157 0173plusmn216 -------- ----------- Before
156plusmn0251 43204plusmn3322 0936plusmn0162 43211plusmn3334 0473plusmn0037 43469plusmn43964 0300plusmn0028 43341plusmn080 0190plusmn0137 43400plusmn43642 050
166plusmn0079 43323plusmn3311 157plusmn0178 43419plusmn3301 137plusmn0115 43311plusmn33022 0883plusmn0054 43341plusmn 133 0616plusmn0153 43120plusmn3301 1
254plusmn0272 43361plusmn3391 222plusmn0093 4331plusmn3390 243plusmn0180 43209plusmn3309 183plusmn0149 43310plusmn2340 128plusmn0153 43312plusmn3390 2
181plusmn0136 43339plusmn3316 161plusmn0129 433plusmn3329 144plusmn0100 43412plusmn3349 0821plusmn0072 0063plusmn0977 0654plusmn0065 43400plusmn4306 4
160plusmn0177 43393plusmn336 152plusmn0200 43416plusmn331 135plusmn0118 4332plusmn3322 0897plusmn0052 43304plusmn3330 0212plusmn0022 43460plusmn43112 6
153plusmn0049 43291plusmn234 163plusmn0242 43346plusmn3300 0891plusmn0272 43306plusmn3310 108plusmn0071 43416plusmn04310 0229plusmn0046 43490plusmn43916 8
340plusmn0522 43214plusmn2341 249plusmn0150 43112plusmn3393 186plusmn0159 43320plusmn336 0773plusmn0094 43390plusmn 134 0264plusmn0043 43400plusmn 54369 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
Table (10) Ceftriaxone clearancecreatinine clearance following repeated ntramuscular injection of 20 mg
ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats
(n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
0934plusmn0083 0305plusmn0013 183plusmn0116 0864plusmn0098 0358plusmn0018 0279plusmn0047 0099plusmn0020 0127plusmn0001 ------- ----------- Before
220plusmn0115 0819plusmn0044 131plusmn00414 0458plusmn0029 0876plusmn0063 126plusmn0068 0361plusmn0011 0813plusmn0031 0018plusmn0003 108plusmn0062 050
164plusmn0078 0818plusmn0029 118plusmn0068 0546plusmn0027 0858plusmn0052 0407plusmn0041 0331plusmn0009 0287plusmn0025 0324plusmn0011 0909plusmn0187 1
161plusmn0044 0488plusmn0005 232plusmn128 0329plusmn0027 169plusmn0464 0686plusmn0050 0409plusmn0020 0220plusmn0029 0512plusmn0077 266plusmn177 2
0933plusmn0024 0394plusmn0005 0948plusmn0062 0296plusmn0007 0381plusmn0027 0160plusmn0008 0235plusmn0014 0083plusmn0006 0528plusmn0028 0362plusmn0041 4
0726plusmn0018 0411plusmn0028 0639plusmn0066 0204plusmn0006 0446plusmn0034 0286plusmn0008 0238plusmn0019 0214plusmn0006 020plusmn0013 0382plusmn0028 6
0609plusmn0072 0425plusmn0036 0508plusmn0052 0192plusmn0009 0524plusmn0146 174plusmn0083 0477plusmn0015 0213plusmn00018 0109plusmn0185 0222plusmn0006 8
108plusmn0128 0496plusmn0012 0942plusmn0004 0265plusmn0030 0891plusmn0056 0706plusmn0103 0351plusmn0022 0354plusmn0018 0111plusmn0021 0098plusmn0018 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
DISCUSSION
In the present investigation intravenous injection of 20 mg ceftriaxonekgbwt in normal goats the drug showed high serum level
(92plusmn 0408 μgml) at 5 minutes post-injection then its concentration was decreased gradually till reached its minimum level (18
plusmn0816μgml) at 8hours post-injection
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
In the present investigation the intravenous injection of 20 mg ceftriaxonekgbwt In normal
goats showed that the drug disposition best fitted a two-compartments- open model a
compartment of plasma and rapid equilibrating tissues and a deeper slower compartment
The obtained result is consistent with those reported for ceftriaxone in lactating goats[9]
lactating ewe[25]
domestic cat[15]
calves[26]
and patanwadi sheep[8]
Also this phenomenon is
in agreement with those reported for other cephalosporines as ceftazidime in a rabbit[27]
cefepime in dog and neonatal foals[28]
ewes[29]
ceftriaxone in goats[9]
cefipime in calves[30]
ceftiofur in cross-bred friesian cattle[31]
cefipime in calves[32]
ceftiofur in cows[33]
cefpirome
in cross-bred calves[3]
cefazidime in goats[35]
and cefquinome in sheep and goats[36]
cefipime
in chickens[37]
Ceftriaxone was distributed after intravenous injection with a distribution phase (α) equal to
656 per hour with a short distribution half ndash life [t05 (α)] equal to 0104 hour The shorter
distribution half-life of ceftriaxone in goats suggested the rapid distribution of the drug in
body tissue and fluid and that nearly similar to that recorded for ceftriaxone in lactating
goats(012 hour)[9]
for ceftriaxone in lactating ewes (0152 hour)[2]
and for ceftriaxone in
calves( 013hour)[26]
The rapid distribution of ceftriaxone in goats is supported by high rate constant of transfer of
the drug from central to peripheral compartment [K12 = 353 h-1
] as compared to the rate
constant of transfer of the drug from peripheral to central compartment [K21= 295 h-1
] This
value is nearly similar to those reported for cefotaxime in goats (K21=327 h-1
)[38]
On contrast
this value was higher than those recorded for ceftriaxone in lactating goats (K21=143 h-1
)[9]
in
lactating ewes (K21=125 h-1
)[25]
and in domestic cats (K21=154 h-1
)[15]
The apparent volume of distribution of ceftriaxone was (0355plusmn0004LKg) this value is
nearly similar to that recorded for cefaronide in sheep(039 LKg)[7]
cefotaxime in dog (048
lkg)[39]
in goat (051 lkg)
[40] for caphalexin in buffalo calves (041 Lkg)
[41] for cefipime in
ewes and calves (032 lkg) (043Lkg)[29]
and[30]
respectively For ceftriaxone in domestic
cats (057Lkg)[15]
in camel (032Lkg)[42]
On the other hand this result is differ than that
reported for cefotaxime in buffalo calves (117Lkg)[43]
High value of the volume of
distribution suggested extensive penetration power Drug with volume of distribution greater
than one literkilogram indicated wide distribution or extensive tissue binding or both[44]
The
apparent volume of distribution in the present study indicated moderate tissue penetrating
power This result agreed with[15]
for ceftriaxone in domestic cats
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
Ceftriaxone is eliminated in the current study following a single intravenous injection with
elimination half ndashlife [t 05(β)] equal to 519 hours This observation is nearly agreed with the
data recorded for ceftizoxime in goats (624hours)[45]
On contrast this value was longer than
that reported for ceftriaxone in lactating ewe (175hours)[25]
for cefaronide in sheep (17
hours)[7]
For cephalexin in buffulo calves (216hours)[41]
for ceftriaxone in healthy horse
(162hours)[46]
also this value is longer than that recorded for ceftriaxone in lactating goats
(144hours)[9]
for cefipime in goats (186hours)[47]
The rate of total body clearance of ceftriaxone following a single intravenous injection is
0048 lkgh which equal to data reported for ceftizoxime in lactating goats (005Lkgh)[45]
On contrast this value is lower than that reported for ceftriaxone in buffulo calves lactating
goats buffulo calves (Bubalus bubalis) goats (capra hircus) patanwadi sheep (026 Lkgh)
(395 Lkgh) (440 Lkgh) (450 Lkgh) (391 Lkgh)[12913118]
respectively
The variation in total body clearance might be attributed to specific interspecies variation
handling of the drug method used healthy status of the animal[48]
The difference between values calculated for pharmacokinetic parameters may be attributed
to animal species the drug formulation employed the age the size or sex o l lf the animal
or even inter individual variation and also due to method of analysis of the drug[49]
Following a single intramuscular injection of 20 mg ceftriaxonekg bwt In normal goats the
drug reached its peak serum concentrations after one hour of injection with value
of(41μgml) Ceftriaxone could be detected in serum in a therapeutic level (263μgml) at 12
hours post-injection The reported peak serum concentrations neerly similar to that reported
for cephalexin in buffulo calves (457 microgml)[41]
These results is differed than those reported
for ceftriaxone in cross breed calves (188 microgml at 30 min[16]
in Kangro breed of goats
(Capra Hircus) (2640 microgml at 20 min[10][50]
found after intramuscular administration of
ceforazone peak plasma concentration was (976 microgml) at 45min This result was also higher
than that recorded for ceftriaxone in buffalo calves (158 microgml)[13]
The calculated maximum serum concentration (Cmax) is (40015 microgml) at maximum time
(tmax) of 157 hours The reported (Cmax) agreed with the data reported for cefipime in goats
(4932 microgml[47]
The reported maximum serum concentration (Cmax) is higher than that
reported for ceftriaxone in lactating goats(236 microgml)[9]
in lactating ewes (1722 microgml[25]
in
wwwwjppscom Vol 5 Issue 01 2016
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
goats (2151 microgml)[11]
for cefquinome in camels (123 microgml)[51]
for ceftriaxone in calves
(1534 microgml)[26]
in patanwadi sheep (1553 microgml)[8]
for cefpirome in cattle (101 microgml)[52]
And for ceftiofur in chickens (2594 μgml)[37]
On the other hand the result was lower than
that reported by[6]
who observed the maximum serum concentration (Cmax) of ceftriaxone in
human after ntramuscular administration was (805 microgml) also it was lower than that
reported for ceftriaxone in dog (11510 microgml)[53]
in domestic cats (5440 microgml)[15]
and for
ceftazoxime in goats (8878 microgml)[45]
The reported [tmax] is neerly similar to that reported for ceftriaxone (104hours)in lactating
ewes by[25]
On contrast it is longer than those reported for ceftriaxone in dogs
(129hours)[53]
for ceftriaxone in lactating goats (07hours)[9]
also the result was longer than
that reported for ceftriaxone in domestic cats (033hours)[15]
in buffulo calves (05 hours)[13]
and for cefpirome in cattle (075hours)[52]
The reported [tmax] is shorter than those reported
for cefquinome in camels (425hours)[51]
in sheep and goats (261 and 262 hours)[36]
and for
ceftiofur in chickens (251 hours)[37]
The elimination half life [t05(β)]
following a single intramuscular administration was 1804 hours This value is nearly agreed
with that recorded for cefquinomein camels (1024hours)[52]
On contrast this result is longer
than that reported for cephalexin in buffalo calves (243hours)[41]
for ceftriaxone in lactating
ewes (177hours)[25]
in buffalo calves (438hours)[13]
in goats (203 hours)[11]
and for
cefipime in goats (165 hours)[47]
The rate of total body clearance of ceftriaxone following a single intramuscular injection is
0043lkgh This value was lower than that reported for ceftriaxone in buffulo calves
(401Lkgh)[13]
in goats (304 Lkgh)[11]
and in sheep (222 Lkgh)[8]
Bioavailability is the fraction of the drug administered by non vascular rout that gains
accesses to the systemic circulation The obtained result revealed that the calculated systemic
bioavailability percent was 6128 It is equal to that recorded for cefpirome in cow calves
(61)[54]
It is nearly equal to that recorded for ceftriaxone in sheep (64)[8]
On the other
hand this value is higher than those recorded for cefperazone in crossbred calves (481)[50]
for ceftriaxone in goats (59)[11]
in calves (47)[55]
On contrast this value is lower than
those reported for cefotaxime in two cats 982 and 93)[57]
for cephradine in goats
wwwwjppscom Vol 5 Issue 01 2016
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
(739)[58]
for ceftazidime in a rabbit (966)[27]
for ceftriaxone in lactating goats (85)[9]
in lactating ewes (836)[25]
in domestic cats 8572[15]
for cefipime in goats 8645[47]
for ceftriaxone in buffulo calves 702[13]
and for ceftiofur in chickens 8890[37]
Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium
infected goats twics dialy for five days revealed that the drug could be detected in a
therapeutic level for 12hours following repeated intramuscular administrations and exceeded
the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]
The relative higher serum concentrations of ceftriaxone after the last dose compared to the
first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12
hours intervals for five consecutive days These observations agreed with data reported by[36]
on comparing the data of serum levels of repeated intramuscular injections with first
intramuscular injection it was revealed that repeated intramuscular injections of cefquinome
have cumulative effect in both species sheep and goats
The obtained result is inconsistent with that reported by[56]
who found thatwhen cefotaxime
was administered repetitively in patients the ratio of maximal serum levels after the last dose
to those after the first dose demonstrated minimal accumulation of intact drug and by[60]
who
found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in
buffalo calves
The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium
infected goats are significantly lower than those in normal goats following repeated
intramuscular injection These lower blood concentrations in Salmonella typhimurium
infected goats might be attributed to the higher penetrating power of ceftriaxone to the
diseased tissues[48]
This phenomenon is similar to data recorded by[61]
who suggested that
Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of
ceftriaxone These alterations might be due to fever and inflammation induced by
infections[59]
proved that the serum concentrations of cephradine following intramuscular
administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after
each intramuscular dose with a lower significant values recorded in Escherichia-coli infected
goats than in normal goatsAlso similer to that reported by[62]
who observed that the
maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep
wwwwjppscom Vol 5 Issue 01 2016
1451
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
in comparison to normal sheepOn contrast[43]
reported that peak plasma level of cefotaxime
in febrile buffalo calves was higher than healthy buffalo calves
In this study the total body clearance (CLtot) in normal goats are significantly lower than in
Salmonella typhimurium infected goats This result supported by[61]
and[63]
fever and
inflammation are cardinal features in bacterial infection which may in turn caused an
increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all
these could lead to increased in the rate at which the drug was delivered to both organs which
were important sites of drug excretion This might somewhat explain the increase in the total
body clearance in infected goats This result is differ than that reported by[64]
who observed
that the clearance of ceftriaxone was significantly reduced in infected mice than in non
infected animals
The highest concentrations of ceftriaxone in milk are recorded 4 hours after each
intramuscular injection with a significant lower value in Salmonella typhimurium infected
goats than in normal goats This might be attributed to accumulation of drug in the inflammed
tissues[48]
This result is similar to those reported by[6559]
who found that milk concentrations
of gentamicin and cephradine were significantly lower in infected goats and cattle than in
normal ones respectively
The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the
non-ionic passive diffusion principle[66]
reported that most drug cross-lipid membranes by
passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly
influenced by the physicochemical properties of the drug[6768]
Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum
ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the
physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]
Milk
contains substantially more lipid and less protein than serum and is slightly more acidic
Therefore drugs which tend to concentrated in milk are weak bases with low serum protein
binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide
and aminothiazole also possesses an hydroxytriazinone group as new and additional
ionization center[70]
these compounds are sufficiently lipid- soluble to be able to penetrate
tissues
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
The dose of ceftriaxone used in the present study induced therapeutically concentrations in
milk These concentrations suggested that ceftriaxone would be efficacious in treatment of
mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily
for 3-5 days
The study showed that the urine concentrations of ceftriaxone are greater than the concurrent
serum concentrations following intramuscular injection This observation is similar to those
reported in cows after cephapirin administrations[71]
In the present study urine concentrations of ceftriaxone increased with the repetition of
dosing This observation supported by[72]
after repeated intramuscular administrations of
ceftriaxone in healthy volunteeres
The mean peak urine concentrations of ceftriaxone were reached 2 hours after each
intramuscular injection The lower urine ceftriaxone concentrations in Salmonella
typhimurium infected goats than in normal goats might be attributed to the accumulation of
the drug in the inflamed tissues[48]
The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower
ratio in Salmonella typhimurium infected goats than in normal goats at different time of
sampling This indicates that glomerular filteration seemed to be the main pathway of
ceftriaxone elimination This observation supported by[59]
who found that the ratio between
cephradine clearance from blood of goats to creatinine clearance showed a marked decrease
in Escherichia-coli infected goats than in normal goats This indicated that glomerular
filteration seemed to be the main pathway of cephradine elimination with a limited rate of
tubular reabsorption
CONCLUSION
The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value
referred a better absorption of ceftriaxone from its site of intramuscular administration The
high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular
administrations suggested that ceftriaxone could be used for treatment of mastitis caused by
Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats
The high concentrations of ceftriaxone in urine after repeated intramuscular administrations
suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in
goats
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Pharmacokinetics of ceftriaxone in calves Veterinarski arhiv 80(1) 1-9
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Pharmacokinetics of cefotaxime and its metabolites in subjects with normal and impaired
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59 Soback S and Ziv G (1988) Pharmacokinetics and bioavailability of ceftriaxone
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J Basic Applied Sci 19(1) 49-54
62 Ranjan R Birendra K R Amita R and Sanjeet K S (2011) Effect of Effect of E coli E
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63 Etuk EU and Onyeyili PA (2006) The effect of Salmonella infection on the plasma
kinetic of chloramphenicol in the sokoto red goats Inter J Pharmacol 2(1) 28-32
64 Wang E Bergeron Y and Bergeron MG (2005) Ceftriaxone pharmacokinetics in
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65 El-Sayed MG Hatem ME and El-Komy AA (1989) Disposition kinetic of
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66 Aramyona JJ Mora J Fraile LJ Garcia MA Abadia AR and Breganate MA
(1996) Penetration of enrofloxacin and ciprofloxacin into breast milk and
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57(4) 547-553
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68 Alkinson A and Begg E (1990) Prediction of drug distribution into human milk from
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sodium cephapirin in lactating dairy cows Am J Vet Res 49(11) 1888-1890
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Ceftriaxone pharmacokinetics following multiple intramuscular dosing Euro J Clin
Pharmacol 30(1) 109-112
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Table (2) Pharmacokinetic parameters of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected
goats following repeated ntramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)
Dose
Unit
عىهParameters
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1269plusmn0073 7409plusmn121 1352plusmn0132 6373plusmn147 1410plusmn0243 5923plusmn126 1461plusmn0214 5430plusmn125 1424plusmn0172 7635plusmn176 gmlmicro A
0651plusmn0049 plusmn000843116 0720plusmn0008 plusmn00413300 0823plusmn0006 plusmn00263322 0848plusmn0025 plusmn00233323 0786plusmn0028 133plusmn0033 h-1 Α
106plusmn0008 330plusmn0015 0962plusmn0011 0392plusmn0007 0841plusmn0007 0567plusmn012 0818plusmn0024 0569plusmn0012 0885plusmn0030 plusmn00124322 H T05(α)
248plusmn0019 168plusmn0047 203plusmn0075 181plusmn0033 267plusmn0039 120plusmn0028 248plusmn0060 122plusmn0026 222plusmn0100 136plusmn0027 h-1 Kab
0278plusmn0002 0412plusmn0009 0342plusmn0012 0383plusmn0008 0252plusmn0009 0567plusmn0011 0279plusmn0005 00569plusmn0011 0314plusmn0014 0 510plusmn0012 H T05(ab)
0627plusmn0008 0378plusmn0007 0430plusmn0008 0402plusmn0008 0113plusmn00027 0424plusmn0009 0117plusmn0004 0394plusmn0008 0116plusmn0003 0239plusmn0005 h-1 K12
121plusmn0013 0962plusmn0022 141plusmn0021 130plusmn0023 0666plusmn0019 0651plusmn0013 0683plusmn0020 0660plusmn0013 0761plusmn0039 0998plusmn0023 h-1 K21
115plusmn0035 129plusmn0026 104plusmn0047 112plusmn0024 106plusmn0037 122plusmn0025 110plusmn0077 119plusmn0023 0910plusmn0032 123plusmn0023 H Tmax
4182plusmn0628 6108plusmn140 3440plusmn0363 5135plusmn0860 3117plusmn0965 4774plusmn0854 2713plusmn0781 4243plusmn0 870 2479plusmn0547 4065plusmn0825 gmlmicro Cmax
4944plusmn0820 7195plusmn142 4199plusmn0702 6511plusmn130 3190plusmn0688 5117plusmn113 3185plusmn0909 4709plusmn0990 3256plusmn0918 6329plusmn139 gmlmicro B
0164plusmn0003 0189plusmn00043 0181plusmn0002 0178plusmn0004 0181plusmn00035 0167plusmn0004 0214plusmn0009 0195plusmn0005 0249plusmn0918 0272plusmn0006 h-1 β
423plusmn0079 367plusmn0086 381plusmn0047 388plusmn0089 382plusmn0074 415plusmn0081 325plusmn0139 355plusmn0075 277plusmn0056 255plusmn0050 H T05β
0879plusmn0015 0429plusmn0009 109plusmn0004 0426plusmn0009 133plusmn0022 0503plusmn0011 154plusmn0064 0675plusmn0013 171plusmn0060 0693plusmn0014 Lkgh Cltot
28358plusmn215 40775plusmn808 21784plusmn0888 34259plusmn720 17860plusmn155 30705plusmn601 15281plusmn239 24135plusmn555 12175plusmn144 20292plusmn487 gmlhmicro AUC
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (3) Milk concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats
following repeated ntramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)
Dose Time of
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
197plusmn0205 200plusmn0408 125plusmn0104 155plusmn0132 0887plusmn0013 0885plusmn014 0500plusmn0040 074plusmn0012 ------------ ------ Before
200plusmn0408 22plusmn0108 197plusmn0205 200plusmn0408 155plusmn0132 197plusmn0205 100plusmn000 155plusmn0132 ----------- -------- 050
526plusmn0166 700plusmn0408 300plusmn0408 64plusmn0163 25plusmn0204 600plusmn0408 155plusmn0132 582plusmn0118 100plusmn000 520plusmn0166 1
640plusmn0163 900plusmn0408 582plusmn0118 792plusmn0114 582plusmn0118 755plusmn0221 275plusmn0061 700plusmn0408 200plusmn0408 691plusmn0176 2
900plusmn0408 1512plusmn0125 640plusmn0163 1475plusmn0322 640plusmn0163 1400plusmn0408 600plusmn0408 1352plusmn0205 526plusmn166 1225plusmn0595 4
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
350plusmn0353 400plusmn0408 300plusmn0408 392plusmn0125 300plusmn0408 35plusmn0353 275plusmn006 300plusmn0408 155plusmn0132 275plusmn0061 6
300 plusmn0408 35plusmn0353 125plusmn0104 200plusmn0408 125plusmn0104 155plusmn01 0825plusmn0062 100plusmn000 0500plusmn0040 0887plusmn0013 8
200plusmn0408 22plusmn0108 100plusmn000 155plusmn0132 100plusmn000 125plusmn0104 0730plusmn002 0825plusmn0078 0422plusmn000 073plusmn0020 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (4) Milkserum concentrations ratios of ceftriaxone in normal and experimentally Salmonella typhimurim infected
goats following repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice daily for five consecutive days (n=4)
Dose Time of
a
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
0400plusmn0049 025plusmn0063 0307plusmn0026 021plusmn0019 0365plusmn00064 016plusmn0026 0232plusmn0016 0205plusmn0002 -------- helliphelliphelliphellip Before
0057plusmn0125 0042plusmn00025 0062plusmn00062 0042plusmn0010 0575plusmn00062 0055plusmn0006 0067plusmn0016 0049plusmn0005 --------- -------- 050
0127plusmn00062 0115plusmn00064 008plusmn0012 0117plusmn0004 0088plusmn00054 0122plusmn0008 008plusmn0017 0126plusmn0028 0039plusmn0005 0122plusmn0004 1
018plusmn0008 0185plusmn0010 021plusmn0004 017plusmn0004 0182plusmn0054 0179plusmn0006 0112plusmn00025 0193plusmn0012 0097plusmn0020 019plusmn0004 2
0357plusmn0020 0425plusmn0005 033plusmn0021 045plusmn0009 0285plusmn0082 0494plusmn0015 0395plusmn0016 0572plusmn001 0415plusmn0017 054plusmn0027 4
018plusmn0015 016plusmn0016 0207plusmn0022 0175plusmn0006 0257plusmn0037 0180plusmn0017 0272plusmn0015 0201plusmn003 0196plusmn0016 0222plusmn0002 6
0212plusmn0033 0212plusmn0020 0200plusmn0044 0122plusmn0024 0152plusmn0011 014plusmn0022 0122plusmn00062 0102plusmn0001 0107plusmn00094 0117plusmn0002 8
0372plusmn0042 025plusmn001 0325plusmn0027 0192plusmn0014 0265plusmn00064 0185plusmn0015 0272plusmn0125 0195plusmn0012 0252plusmn0032 0275plusmn0009 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
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Table (5) The amount of urine (mlmin) voided in normal and experimentally Salmonella typhimurim infected goats following
repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)
Dose Time of a
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
plusmn00372344 126plusmn0034 130plusmn0030 130plusmn0028 118plusmn0066 118plusmn0067 108plusmn0013 108plusmn0008 ----------- -------- Before
0577plusmn0069 43494057plusmn 045plusmn0060 plusmn0064309 0312plusmn002 033plusmn0012 0340plusmn0024 033plusmn0012 0287plusmn0017 0272plusmn0014 050
0712plusmn0019 0692plusmn0014 068plusmn0081 0697plusmn0006 0672plusmn0011 0675plusmn 0009 0635plusmn0032 0655plusmn0010 0719plusmn0031 0697plusmn0015 1
0837plusmn0025 0787plusmn0021 0732plusmn0011 plusmn00054300 0715plusmn0011 0715plusmn002 0722plusmn0019 0702plusmn0018 0737plusmn0027 0762plusmn0041 2
0535plusmn0095 0507plusmn0021 0447plusmn0022 0452plusmn002 0402plusmn0075 0405plusmn0011 0400plusmn0057 0397plusmn0009 0380plusmn0004 038plusmn001 4
0437plusmn00094 0432plusmn0008 0400plusmn0010 0405plusmn0002 0380plusmn0007 plusmn00044319 0372plusmn0047 037plusmn 0007 0350plusmn0005 0365plusmn0006 6
0397plusmn0028 0410plusmn0008 0380plusmn0012 0395plusmn0009 0355plusmn0086 0352plusmn0007 0340plusmn0004 0345plusmn0005 0302plusmn0004 0335plusmn0005 8
0385plusmn001 0380plusmn0010 0385plusmn00064 0380plusmn0008 0365plusmn0064 0367plusmn0004 0362plusmn0086 0372plusmn0106 0327plusmn0006 0362plusmn0016 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (6) Urine concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats
following repeated intramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)
Dose Time of a
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1125plusmn150 1125plusmn15 735plusmn287 81plusmn324 183plusmn03 555plusmn798 37plusmn0811 1815plusmn43290 -------------- ------ Before
2415plusmn357 2625plusmn374 1695plusmn788 249plusmn574 10575plusmn64 2415plusmn357 5400plusmn273 2085plusmn991 102plusmn160 168plusmn547 050
26025plusmn787 2923plusmn479 22425plusmn1225 2805plusmn35 1695plusmn618 2705plusmn471 10200plusmn547 2415plusmn357 6975plusmn225 22425plusmn894 1
29295plusmn765 3012plusmn346 28575plusmn738 2964plusmn415 2355plusmn259 2923plusmn479 1635plusmn561 2645plusmn917 102plusmn547 24825plusmn616 2
23475plusmn430 2482plusmn616 23475plusmn1564 2415plusmn357 1695plusmn788 198plusmn848 8475plusmn309 1515plusmn708 60plusmn212 1185plusmn45 4
1905plusmn45 2355plusmn259 153plusmn519 1935plusmn960 114plusmn948 159plusmn173 6675plusmn309 1215plusmn45 1312plusmn0552 855plusmn193 6
153plusmn1024 1965plusmn135 1335plusmn1229 150plusmn34 735plusmn295 1365plusmn665 6181plusmn339 72plusmn244 907plusmn0951 5025plusmn143 8
135plusmn519 120plusmn346 11725plusmn1551 96plusmn874 525plusmn295 75plusmn173 153plusmn130 39plusmn212 3735plusmn0458 13125plusmn0552 12
Between normal and diseased
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (7) Urineserum concentrations ratios of ceftriaxone following repeated ntramuscular injection of 20 mg
ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats
(n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
229plusmn 163 1448plusmn0743 1885plusmn159 1125plusmn0484 533plusmn0260 1050plusmn358 175plusmn0380 4146plusmn116 ------- ------ Before
741plusmn0063 plusmn01553 58plusmn0242 plusmn0149390 422plusmn0206 683plusmn0106 245plusmn0092 667plusmn0306 0510plusmn0081 559plusmn0181 050
651plusmn0243 plusmn0065031 637plusmn0373 plusmn014431 565plusmn0243 plusmn0085300 360plusmn0303 plusmn0110312 279plusmn0121 534plusmn0248 1
836plusmn0150 plusmn00476322 862plusmn0180 plusmn010463 942plusmn0166 plusmn0130631 217plusmn0303 727plusmn0256 508plusmn0186 plusmn01680340 2
939plusmn0235 plusmn01580344 1006plusmn0710 plusmn00750310 999plusmn0542 plusmn02850344 565plusmn0223 641plusmn0241 48plusmn0164 plusmn014834 4
1005plusmn0418 2plusmn018813 1097plusmn0641 plusmn03979300 993plusmn0921 plusmn0252931 619plusmn0483 plusmn0362933 167plusmn0101 642plusmn0644 6
1091plusmn0649 plusmn075332339 1171plusmn0980 995plusmn0415 925plusmn0593 plusmn05593433 886plusmn0408 plusmn02510311 2055plusmn0311 plusmn02046310 8
2392plusmn129 plusmn032731396 1794plusmn0228 1222plusmn124 1418plusmn109 plusmn026733336 580plusmn0397 plusmn03951326 227plusmn0452 plusmn02740316 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (8) Creatinine clearance (mlmin10kgbwt) following repeated intramuscular injection of 20 mg ceftriaxonekgbwt
twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats (n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1115plusmn0703 2265plusmn167 481plusmn0409 672plusmn0817 669plusmn0672 1202plusmn0777 695plusmn0634 1724plusmn179 ----------- ------ Before
0703plusmn0091 147plusmn0305 0718plusmn0141 251plusmn0707 0547plusmn0055 0699plusmn0092 0802plusmn0099 103plusmn0106 295plusmn0124 0458plusmn0037 050
101plusmn0075 161plusmn0093 131plusmn0099 264plusmn0217 161plusmn0146 373plusmn0499 247plusmn0110 4755plusmn0582 214plusmn0234 103plusmn0166 1
157plusmn0198 387plusmn0340 173plusmn0501 267plusmn0217 187plusmn0563 287plusmn0499 451plusmn0223 972plusmn105 263plusmn0399 169plusmn0454 2
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
184plusmn0095 346plusmn0444 173plusmn0501 436plusmn0599 383plusmn0299 682plusmn0584 328plusmn0253 119plusmn153 123plusmn0057 292plusmn0742 4
221plusmn0242 411plusmn0661 241plusmn0186 663plusmn0584 308plusmn0234 422plusmn0314 353plusmn0393 548plusmn0901 105plusmn0057 264plusmn0294 6
261plusmn0295 476plusmn0339 319plusmn0273 753plusmn0676 106plusmn0207 0773plusmn0049 228plusmn0175 456plusmn0340 206plusmn0160 404plusmn0419 8
310plusmn0218 409plusmn0434 3264plusmn0153 669plusmn0476 209plusmn0189 235plusmn0337 217plusmn0143 377plusmn0342 240plusmn0218 6055plusmn0176 12
Between normal and diseased
Plt 005 Plt001 Plt0001
Table (9) Ceftriaxone clearance (mlmin10kgbwt following repeated intramuscular injection of 20 mg ceftriaxone kgbwt
twice in normal and experimentally Salmonella typhimurim infected goats (n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1048plusmn121 0557plusmn684 895plusmn113 0547plusmn560 238plusmn0222 103plusmn 480 0668plusmn0157 0173plusmn216 -------- ----------- Before
156plusmn0251 43204plusmn3322 0936plusmn0162 43211plusmn3334 0473plusmn0037 43469plusmn43964 0300plusmn0028 43341plusmn080 0190plusmn0137 43400plusmn43642 050
166plusmn0079 43323plusmn3311 157plusmn0178 43419plusmn3301 137plusmn0115 43311plusmn33022 0883plusmn0054 43341plusmn 133 0616plusmn0153 43120plusmn3301 1
254plusmn0272 43361plusmn3391 222plusmn0093 4331plusmn3390 243plusmn0180 43209plusmn3309 183plusmn0149 43310plusmn2340 128plusmn0153 43312plusmn3390 2
181plusmn0136 43339plusmn3316 161plusmn0129 433plusmn3329 144plusmn0100 43412plusmn3349 0821plusmn0072 0063plusmn0977 0654plusmn0065 43400plusmn4306 4
160plusmn0177 43393plusmn336 152plusmn0200 43416plusmn331 135plusmn0118 4332plusmn3322 0897plusmn0052 43304plusmn3330 0212plusmn0022 43460plusmn43112 6
153plusmn0049 43291plusmn234 163plusmn0242 43346plusmn3300 0891plusmn0272 43306plusmn3310 108plusmn0071 43416plusmn04310 0229plusmn0046 43490plusmn43916 8
340plusmn0522 43214plusmn2341 249plusmn0150 43112plusmn3393 186plusmn0159 43320plusmn336 0773plusmn0094 43390plusmn 134 0264plusmn0043 43400plusmn 54369 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
Table (10) Ceftriaxone clearancecreatinine clearance following repeated ntramuscular injection of 20 mg
ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats
(n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
0934plusmn0083 0305plusmn0013 183plusmn0116 0864plusmn0098 0358plusmn0018 0279plusmn0047 0099plusmn0020 0127plusmn0001 ------- ----------- Before
220plusmn0115 0819plusmn0044 131plusmn00414 0458plusmn0029 0876plusmn0063 126plusmn0068 0361plusmn0011 0813plusmn0031 0018plusmn0003 108plusmn0062 050
164plusmn0078 0818plusmn0029 118plusmn0068 0546plusmn0027 0858plusmn0052 0407plusmn0041 0331plusmn0009 0287plusmn0025 0324plusmn0011 0909plusmn0187 1
161plusmn0044 0488plusmn0005 232plusmn128 0329plusmn0027 169plusmn0464 0686plusmn0050 0409plusmn0020 0220plusmn0029 0512plusmn0077 266plusmn177 2
0933plusmn0024 0394plusmn0005 0948plusmn0062 0296plusmn0007 0381plusmn0027 0160plusmn0008 0235plusmn0014 0083plusmn0006 0528plusmn0028 0362plusmn0041 4
0726plusmn0018 0411plusmn0028 0639plusmn0066 0204plusmn0006 0446plusmn0034 0286plusmn0008 0238plusmn0019 0214plusmn0006 020plusmn0013 0382plusmn0028 6
0609plusmn0072 0425plusmn0036 0508plusmn0052 0192plusmn0009 0524plusmn0146 174plusmn0083 0477plusmn0015 0213plusmn00018 0109plusmn0185 0222plusmn0006 8
108plusmn0128 0496plusmn0012 0942plusmn0004 0265plusmn0030 0891plusmn0056 0706plusmn0103 0351plusmn0022 0354plusmn0018 0111plusmn0021 0098plusmn0018 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
DISCUSSION
In the present investigation intravenous injection of 20 mg ceftriaxonekgbwt in normal goats the drug showed high serum level
(92plusmn 0408 μgml) at 5 minutes post-injection then its concentration was decreased gradually till reached its minimum level (18
plusmn0816μgml) at 8hours post-injection
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
In the present investigation the intravenous injection of 20 mg ceftriaxonekgbwt In normal
goats showed that the drug disposition best fitted a two-compartments- open model a
compartment of plasma and rapid equilibrating tissues and a deeper slower compartment
The obtained result is consistent with those reported for ceftriaxone in lactating goats[9]
lactating ewe[25]
domestic cat[15]
calves[26]
and patanwadi sheep[8]
Also this phenomenon is
in agreement with those reported for other cephalosporines as ceftazidime in a rabbit[27]
cefepime in dog and neonatal foals[28]
ewes[29]
ceftriaxone in goats[9]
cefipime in calves[30]
ceftiofur in cross-bred friesian cattle[31]
cefipime in calves[32]
ceftiofur in cows[33]
cefpirome
in cross-bred calves[3]
cefazidime in goats[35]
and cefquinome in sheep and goats[36]
cefipime
in chickens[37]
Ceftriaxone was distributed after intravenous injection with a distribution phase (α) equal to
656 per hour with a short distribution half ndash life [t05 (α)] equal to 0104 hour The shorter
distribution half-life of ceftriaxone in goats suggested the rapid distribution of the drug in
body tissue and fluid and that nearly similar to that recorded for ceftriaxone in lactating
goats(012 hour)[9]
for ceftriaxone in lactating ewes (0152 hour)[2]
and for ceftriaxone in
calves( 013hour)[26]
The rapid distribution of ceftriaxone in goats is supported by high rate constant of transfer of
the drug from central to peripheral compartment [K12 = 353 h-1
] as compared to the rate
constant of transfer of the drug from peripheral to central compartment [K21= 295 h-1
] This
value is nearly similar to those reported for cefotaxime in goats (K21=327 h-1
)[38]
On contrast
this value was higher than those recorded for ceftriaxone in lactating goats (K21=143 h-1
)[9]
in
lactating ewes (K21=125 h-1
)[25]
and in domestic cats (K21=154 h-1
)[15]
The apparent volume of distribution of ceftriaxone was (0355plusmn0004LKg) this value is
nearly similar to that recorded for cefaronide in sheep(039 LKg)[7]
cefotaxime in dog (048
lkg)[39]
in goat (051 lkg)
[40] for caphalexin in buffalo calves (041 Lkg)
[41] for cefipime in
ewes and calves (032 lkg) (043Lkg)[29]
and[30]
respectively For ceftriaxone in domestic
cats (057Lkg)[15]
in camel (032Lkg)[42]
On the other hand this result is differ than that
reported for cefotaxime in buffalo calves (117Lkg)[43]
High value of the volume of
distribution suggested extensive penetration power Drug with volume of distribution greater
than one literkilogram indicated wide distribution or extensive tissue binding or both[44]
The
apparent volume of distribution in the present study indicated moderate tissue penetrating
power This result agreed with[15]
for ceftriaxone in domestic cats
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Ceftriaxone is eliminated in the current study following a single intravenous injection with
elimination half ndashlife [t 05(β)] equal to 519 hours This observation is nearly agreed with the
data recorded for ceftizoxime in goats (624hours)[45]
On contrast this value was longer than
that reported for ceftriaxone in lactating ewe (175hours)[25]
for cefaronide in sheep (17
hours)[7]
For cephalexin in buffulo calves (216hours)[41]
for ceftriaxone in healthy horse
(162hours)[46]
also this value is longer than that recorded for ceftriaxone in lactating goats
(144hours)[9]
for cefipime in goats (186hours)[47]
The rate of total body clearance of ceftriaxone following a single intravenous injection is
0048 lkgh which equal to data reported for ceftizoxime in lactating goats (005Lkgh)[45]
On contrast this value is lower than that reported for ceftriaxone in buffulo calves lactating
goats buffulo calves (Bubalus bubalis) goats (capra hircus) patanwadi sheep (026 Lkgh)
(395 Lkgh) (440 Lkgh) (450 Lkgh) (391 Lkgh)[12913118]
respectively
The variation in total body clearance might be attributed to specific interspecies variation
handling of the drug method used healthy status of the animal[48]
The difference between values calculated for pharmacokinetic parameters may be attributed
to animal species the drug formulation employed the age the size or sex o l lf the animal
or even inter individual variation and also due to method of analysis of the drug[49]
Following a single intramuscular injection of 20 mg ceftriaxonekg bwt In normal goats the
drug reached its peak serum concentrations after one hour of injection with value
of(41μgml) Ceftriaxone could be detected in serum in a therapeutic level (263μgml) at 12
hours post-injection The reported peak serum concentrations neerly similar to that reported
for cephalexin in buffulo calves (457 microgml)[41]
These results is differed than those reported
for ceftriaxone in cross breed calves (188 microgml at 30 min[16]
in Kangro breed of goats
(Capra Hircus) (2640 microgml at 20 min[10][50]
found after intramuscular administration of
ceforazone peak plasma concentration was (976 microgml) at 45min This result was also higher
than that recorded for ceftriaxone in buffalo calves (158 microgml)[13]
The calculated maximum serum concentration (Cmax) is (40015 microgml) at maximum time
(tmax) of 157 hours The reported (Cmax) agreed with the data reported for cefipime in goats
(4932 microgml[47]
The reported maximum serum concentration (Cmax) is higher than that
reported for ceftriaxone in lactating goats(236 microgml)[9]
in lactating ewes (1722 microgml[25]
in
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
goats (2151 microgml)[11]
for cefquinome in camels (123 microgml)[51]
for ceftriaxone in calves
(1534 microgml)[26]
in patanwadi sheep (1553 microgml)[8]
for cefpirome in cattle (101 microgml)[52]
And for ceftiofur in chickens (2594 μgml)[37]
On the other hand the result was lower than
that reported by[6]
who observed the maximum serum concentration (Cmax) of ceftriaxone in
human after ntramuscular administration was (805 microgml) also it was lower than that
reported for ceftriaxone in dog (11510 microgml)[53]
in domestic cats (5440 microgml)[15]
and for
ceftazoxime in goats (8878 microgml)[45]
The reported [tmax] is neerly similar to that reported for ceftriaxone (104hours)in lactating
ewes by[25]
On contrast it is longer than those reported for ceftriaxone in dogs
(129hours)[53]
for ceftriaxone in lactating goats (07hours)[9]
also the result was longer than
that reported for ceftriaxone in domestic cats (033hours)[15]
in buffulo calves (05 hours)[13]
and for cefpirome in cattle (075hours)[52]
The reported [tmax] is shorter than those reported
for cefquinome in camels (425hours)[51]
in sheep and goats (261 and 262 hours)[36]
and for
ceftiofur in chickens (251 hours)[37]
The elimination half life [t05(β)]
following a single intramuscular administration was 1804 hours This value is nearly agreed
with that recorded for cefquinomein camels (1024hours)[52]
On contrast this result is longer
than that reported for cephalexin in buffalo calves (243hours)[41]
for ceftriaxone in lactating
ewes (177hours)[25]
in buffalo calves (438hours)[13]
in goats (203 hours)[11]
and for
cefipime in goats (165 hours)[47]
The rate of total body clearance of ceftriaxone following a single intramuscular injection is
0043lkgh This value was lower than that reported for ceftriaxone in buffulo calves
(401Lkgh)[13]
in goats (304 Lkgh)[11]
and in sheep (222 Lkgh)[8]
Bioavailability is the fraction of the drug administered by non vascular rout that gains
accesses to the systemic circulation The obtained result revealed that the calculated systemic
bioavailability percent was 6128 It is equal to that recorded for cefpirome in cow calves
(61)[54]
It is nearly equal to that recorded for ceftriaxone in sheep (64)[8]
On the other
hand this value is higher than those recorded for cefperazone in crossbred calves (481)[50]
for ceftriaxone in goats (59)[11]
in calves (47)[55]
On contrast this value is lower than
those reported for cefotaxime in two cats 982 and 93)[57]
for cephradine in goats
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
(739)[58]
for ceftazidime in a rabbit (966)[27]
for ceftriaxone in lactating goats (85)[9]
in lactating ewes (836)[25]
in domestic cats 8572[15]
for cefipime in goats 8645[47]
for ceftriaxone in buffulo calves 702[13]
and for ceftiofur in chickens 8890[37]
Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium
infected goats twics dialy for five days revealed that the drug could be detected in a
therapeutic level for 12hours following repeated intramuscular administrations and exceeded
the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]
The relative higher serum concentrations of ceftriaxone after the last dose compared to the
first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12
hours intervals for five consecutive days These observations agreed with data reported by[36]
on comparing the data of serum levels of repeated intramuscular injections with first
intramuscular injection it was revealed that repeated intramuscular injections of cefquinome
have cumulative effect in both species sheep and goats
The obtained result is inconsistent with that reported by[56]
who found thatwhen cefotaxime
was administered repetitively in patients the ratio of maximal serum levels after the last dose
to those after the first dose demonstrated minimal accumulation of intact drug and by[60]
who
found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in
buffalo calves
The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium
infected goats are significantly lower than those in normal goats following repeated
intramuscular injection These lower blood concentrations in Salmonella typhimurium
infected goats might be attributed to the higher penetrating power of ceftriaxone to the
diseased tissues[48]
This phenomenon is similar to data recorded by[61]
who suggested that
Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of
ceftriaxone These alterations might be due to fever and inflammation induced by
infections[59]
proved that the serum concentrations of cephradine following intramuscular
administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after
each intramuscular dose with a lower significant values recorded in Escherichia-coli infected
goats than in normal goatsAlso similer to that reported by[62]
who observed that the
maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
in comparison to normal sheepOn contrast[43]
reported that peak plasma level of cefotaxime
in febrile buffalo calves was higher than healthy buffalo calves
In this study the total body clearance (CLtot) in normal goats are significantly lower than in
Salmonella typhimurium infected goats This result supported by[61]
and[63]
fever and
inflammation are cardinal features in bacterial infection which may in turn caused an
increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all
these could lead to increased in the rate at which the drug was delivered to both organs which
were important sites of drug excretion This might somewhat explain the increase in the total
body clearance in infected goats This result is differ than that reported by[64]
who observed
that the clearance of ceftriaxone was significantly reduced in infected mice than in non
infected animals
The highest concentrations of ceftriaxone in milk are recorded 4 hours after each
intramuscular injection with a significant lower value in Salmonella typhimurium infected
goats than in normal goats This might be attributed to accumulation of drug in the inflammed
tissues[48]
This result is similar to those reported by[6559]
who found that milk concentrations
of gentamicin and cephradine were significantly lower in infected goats and cattle than in
normal ones respectively
The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the
non-ionic passive diffusion principle[66]
reported that most drug cross-lipid membranes by
passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly
influenced by the physicochemical properties of the drug[6768]
Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum
ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the
physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]
Milk
contains substantially more lipid and less protein than serum and is slightly more acidic
Therefore drugs which tend to concentrated in milk are weak bases with low serum protein
binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide
and aminothiazole also possesses an hydroxytriazinone group as new and additional
ionization center[70]
these compounds are sufficiently lipid- soluble to be able to penetrate
tissues
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The dose of ceftriaxone used in the present study induced therapeutically concentrations in
milk These concentrations suggested that ceftriaxone would be efficacious in treatment of
mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily
for 3-5 days
The study showed that the urine concentrations of ceftriaxone are greater than the concurrent
serum concentrations following intramuscular injection This observation is similar to those
reported in cows after cephapirin administrations[71]
In the present study urine concentrations of ceftriaxone increased with the repetition of
dosing This observation supported by[72]
after repeated intramuscular administrations of
ceftriaxone in healthy volunteeres
The mean peak urine concentrations of ceftriaxone were reached 2 hours after each
intramuscular injection The lower urine ceftriaxone concentrations in Salmonella
typhimurium infected goats than in normal goats might be attributed to the accumulation of
the drug in the inflamed tissues[48]
The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower
ratio in Salmonella typhimurium infected goats than in normal goats at different time of
sampling This indicates that glomerular filteration seemed to be the main pathway of
ceftriaxone elimination This observation supported by[59]
who found that the ratio between
cephradine clearance from blood of goats to creatinine clearance showed a marked decrease
in Escherichia-coli infected goats than in normal goats This indicated that glomerular
filteration seemed to be the main pathway of cephradine elimination with a limited rate of
tubular reabsorption
CONCLUSION
The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value
referred a better absorption of ceftriaxone from its site of intramuscular administration The
high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular
administrations suggested that ceftriaxone could be used for treatment of mastitis caused by
Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats
The high concentrations of ceftriaxone in urine after repeated intramuscular administrations
suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in
goats
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28 Gardner S Y and Papich M G (2001) Comparison of cefepime pharmacokinetics in
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29 Ismail M (2005a) Pharmacokinetics of cefepime administered by iv and im routes to
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30 Patel U D Bhavsar S K and Thaker A M (2006) Pharmacokinetics and dosage
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31 El-Gendy AAM Tohamy MA and Ismail M (2007) Comparative pharmacokinetic
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32 Joshi B and Kumar Sharma S (2009) The pharmacokinetics of cefepime in E coli
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34 Rajput N Kumar V D and Sandhu HS (2011) Pharmacokinetics and dosage
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35 Abo-El- Sooud K and Tohamy MA (2011) Comparative pharmacokinetics and milk
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36 El-Hewaity M Abd El Latif A Soliman A and Aboubakr M (2014) Comparative
pharmacokinetics of cefquinome (Cobactan 25) following repeated intramuscular
administrations in sheep and goats J Vet Med Doi 949642 1-5
37 El-Sayed M G A El-Komy A A A El barawy A M and Ibrahim D M A (2015)
Pharmacokinetics and tissue residues of ceftiofur in normal and Escherichia coli infected
chickens J Phys Pharm Adv 5(3) 574-582
38 Datta B Mandal TK and Chakraborty A K (2003) Pharmacokinetics of cefotaxime
in goats with experimentally induced kidney damage Ind J pharmacol (35) 173-176
39 Guerrini HV English BP Filippich J L Schneider J and Bourne D W (1986)
The pharmacokinetics of cefotaxime in dog Vet Rec 119(4) 81-83
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40 Atef M Ramadan A Afifi N A and Youssef S A (1990) pharmacokinetic profile
of cefotaxime in goat Res Vet Sci 49(1) 34-38
41 Satish K G Chaudhary RK Srivastiva AK and Garg BD (1990) Pharmacokintics
and dosage regemine of cephalexine in buffulo calves (Bubalis Bubalis following single
intravenous and intramusculer adminsteration Veterinary research commuincation 14
59-62
42 Goudah A (2008) Pharmacokinetic parameters of ceftriaxone after single intravenous
and intramuscular administration in camels (Camelus Dromedarius) Res Vet Sci Jun
84(3) 483-9
43 Sharma SK Srivastava AK and Deore DM (2006) Effect of Ecoli
lipopolysaccharides ndashinduced fever on disposition pattern of cefotaxime in buffalo calves
Veterinarski Arhiv 76(6) 537-545
44 Baggot JD (1977) Priniciple of pharmacokinetics In principle of drug disposition in
domestic animals The physiological Basis of veterinary Clinical Pharmacology 1st ed
WB Saunders Co Philadelphi PA 168-179
45 Karmaker UK Datta BK Patra PH Prashant M Suman S Sar TK Chakaborty
AK and mandal KT (2011) Disposition kinetics of ceftizoxime in healthy and mastitic
goats after intravenous adminsteration Pharmacologyonline 3 935-946
46 Ringger NC Pearson EG Gronwall R Kohlepp S J (1996) Pharmacokinetics of
ceftriaxone in healthy horses Equine Vet J Nov 28(6) 476-9
47 Prawez S Raina R Dimitrova D panka NK Ahanger AA Verma PK (2010) The
pharmacokinetics of cefipime in goats following single dose iv and im adminsteration
Turk j vet Anima Sci 34(5) 427-431
48 Baggot JD (1980) Distribution of antimicrobial agents in normal and diseased animals
JAVMA 19(76) 1085-1090
49 Haddad N S Pedersoli W M Ravis W R Fazeli M H and Carson Jr R L (1985)
Pharmacokinetics of gentamicin at steady-state in ponies serum urine and endometrial
concentrations Am J Vet Res 46(6) 1268-1271
50 Gupta JK Chaudhary RK and Dumka VK (2008) Pharmacokinetics after single
intramuscuker adminsrerarion and in-vitro binding plasma protein of cefoprazone in cross
bred calves Veterinaski Arhiv 78(5) 441-448
51 Al Taher AY (2010) Pharmacokinetics of cefquinome in camels J An Vet Ad 9(4)
848-852
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52 Rajput N Dumka V K and Sandhu HS (2012) Pharmacokinetics and in- vitro
plasma protein binding of cefpirome in cattle Veterinaski Arhiv 82(1) 1-9
53 RebueltoM Albarellos G Ambros L Kreil V Montoya L Bonafine R Otero P
Hallu R (2002) Pharmacokinetics of ceftriaxone administered by the intravenous
intramuscular or subcutaneous routes to dogs J Vet Pharmacol Ther Feb 25(1) 73-6
54 Patel RB Bhavsar SK Solanki PF Patel JH Varia RD Modi Falguni D and
Patel MD (2013) Pharmacokinetics of cefpirome following intravenous and
intramuscular administration in cow calves Sci Int 1(11) 371-374
55 Maradiya J J Goriya H V Bhavsar S K Patel U D and Thaker A M (2010)
Pharmacokinetics of ceftriaxone in calves Veterinarski arhiv 80(1) 1-9
56 Inges R MJ Fillastre J Godin M Leroy A and Humbert G (1982) The
Pharmacokinetics of cefotaxime and its metabolites in subjects with normal and impaired
renal function Clin Infect Dis (4) 379-391
57 Mcelroy D Ravis W R and Clark C H (1986) Pharmacokinetics of cefotaxime in
the domestic cats Am J Vet Res 47(1) 86-88
58 El-Sayed MG Atef M and El-Komy AA (1994) Disposition kinetic of cephradine in
normal and Escherichia coli infected goats Dtsch Tierarztl Wochenschr 101(2) 56-60
59 Soback S and Ziv G (1988) Pharmacokinetics and bioavailability of ceftriaxone
administered intravenously and intramuscularly to calves Am J Vet Res 49 535-538
60 Sharma S K and Srivastava A K (2003) Cefotaxime pharmacokinetics in male
buffalo calves following multiple dosing Veterinarski arhiv 73(4) 191-197
61 Abdulgafar O J Shaibu O B and Emmanuel U E (2011) Effect of Salmonella
typhymurium infection on the pharmacokinetics of ceftriaxone in sokoto red goats Niger
J Basic Applied Sci 19(1) 49-54
62 Ranjan R Birendra K R Amita R and Sanjeet K S (2011) Effect of Effect of E coli E
coli endotoxin induced fever on the pharmacokinetic profile and dosage regimen of
ceftriaxone in sheep (Ovis aries) Veterinarski arhiv 81(4) 423-432
63 Etuk EU and Onyeyili PA (2006) The effect of Salmonella infection on the plasma
kinetic of chloramphenicol in the sokoto red goats Inter J Pharmacol 2(1) 28-32
64 Wang E Bergeron Y and Bergeron MG (2005) Ceftriaxone pharmacokinetics in
interleukin-10-treated murine pneumococcal pneumonia J Antimicrob Chemother 55
721ndash726
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65 El-Sayed MG Hatem ME and El-Komy AA (1989) Disposition kinetic of
gentamicin in normal and endometric cow using microbiological assay Dtsch Tierarztl
Wochenschr 96(8) 412-415
66 Aramyona JJ Mora J Fraile LJ Garcia MA Abadia AR and Breganate MA
(1996) Penetration of enrofloxacin and ciprofloxacin into breast milk and
pharmacokinetics of the drugs in lacating rabbits and neonatal offspring Am J Vet Res
57(4) 547-553
67 Rusmussen F (1966) Studies on the mammary excretion and absorbtion of drugs Vet
Rec (87) 14-18
68 Alkinson A and Begg E (1990) Prediction of drug distribution into human milk from
physicochemical characteristics Clin Pharmacokinet 18(2) 151-167
69 Kenneth F (1997) Drug distribution in human milk Aust Prescr 20(2) 35-40
70 Aleksić M Savić V Popović G Burić N and Kapetanović V (2005) Acidity
constants of cefetamet cefotaxime and ceftriaxone the effect of the substituent at C3
position J Pharm Biomed Anal 39(3-4) 752-756
71 Prades M Brown M P Gronwall R and Miles N S (1988) Pharmacokinetics of
sodium cephapirin in lactating dairy cows Am J Vet Res 49(11) 1888-1890
72 Holazo A A Patel I H Weinfeld R E Konikoff J J and Parsonnet M (1986)
Ceftriaxone pharmacokinetics following multiple intramuscular dosing Euro J Clin
Pharmacol 30(1) 109-112
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350plusmn0353 400plusmn0408 300plusmn0408 392plusmn0125 300plusmn0408 35plusmn0353 275plusmn006 300plusmn0408 155plusmn0132 275plusmn0061 6
300 plusmn0408 35plusmn0353 125plusmn0104 200plusmn0408 125plusmn0104 155plusmn01 0825plusmn0062 100plusmn000 0500plusmn0040 0887plusmn0013 8
200plusmn0408 22plusmn0108 100plusmn000 155plusmn0132 100plusmn000 125plusmn0104 0730plusmn002 0825plusmn0078 0422plusmn000 073plusmn0020 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (4) Milkserum concentrations ratios of ceftriaxone in normal and experimentally Salmonella typhimurim infected
goats following repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice daily for five consecutive days (n=4)
Dose Time of
a
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
0400plusmn0049 025plusmn0063 0307plusmn0026 021plusmn0019 0365plusmn00064 016plusmn0026 0232plusmn0016 0205plusmn0002 -------- helliphelliphelliphellip Before
0057plusmn0125 0042plusmn00025 0062plusmn00062 0042plusmn0010 0575plusmn00062 0055plusmn0006 0067plusmn0016 0049plusmn0005 --------- -------- 050
0127plusmn00062 0115plusmn00064 008plusmn0012 0117plusmn0004 0088plusmn00054 0122plusmn0008 008plusmn0017 0126plusmn0028 0039plusmn0005 0122plusmn0004 1
018plusmn0008 0185plusmn0010 021plusmn0004 017plusmn0004 0182plusmn0054 0179plusmn0006 0112plusmn00025 0193plusmn0012 0097plusmn0020 019plusmn0004 2
0357plusmn0020 0425plusmn0005 033plusmn0021 045plusmn0009 0285plusmn0082 0494plusmn0015 0395plusmn0016 0572plusmn001 0415plusmn0017 054plusmn0027 4
018plusmn0015 016plusmn0016 0207plusmn0022 0175plusmn0006 0257plusmn0037 0180plusmn0017 0272plusmn0015 0201plusmn003 0196plusmn0016 0222plusmn0002 6
0212plusmn0033 0212plusmn0020 0200plusmn0044 0122plusmn0024 0152plusmn0011 014plusmn0022 0122plusmn00062 0102plusmn0001 0107plusmn00094 0117plusmn0002 8
0372plusmn0042 025plusmn001 0325plusmn0027 0192plusmn0014 0265plusmn00064 0185plusmn0015 0272plusmn0125 0195plusmn0012 0252plusmn0032 0275plusmn0009 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
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Table (5) The amount of urine (mlmin) voided in normal and experimentally Salmonella typhimurim infected goats following
repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)
Dose Time of a
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
plusmn00372344 126plusmn0034 130plusmn0030 130plusmn0028 118plusmn0066 118plusmn0067 108plusmn0013 108plusmn0008 ----------- -------- Before
0577plusmn0069 43494057plusmn 045plusmn0060 plusmn0064309 0312plusmn002 033plusmn0012 0340plusmn0024 033plusmn0012 0287plusmn0017 0272plusmn0014 050
0712plusmn0019 0692plusmn0014 068plusmn0081 0697plusmn0006 0672plusmn0011 0675plusmn 0009 0635plusmn0032 0655plusmn0010 0719plusmn0031 0697plusmn0015 1
0837plusmn0025 0787plusmn0021 0732plusmn0011 plusmn00054300 0715plusmn0011 0715plusmn002 0722plusmn0019 0702plusmn0018 0737plusmn0027 0762plusmn0041 2
0535plusmn0095 0507plusmn0021 0447plusmn0022 0452plusmn002 0402plusmn0075 0405plusmn0011 0400plusmn0057 0397plusmn0009 0380plusmn0004 038plusmn001 4
0437plusmn00094 0432plusmn0008 0400plusmn0010 0405plusmn0002 0380plusmn0007 plusmn00044319 0372plusmn0047 037plusmn 0007 0350plusmn0005 0365plusmn0006 6
0397plusmn0028 0410plusmn0008 0380plusmn0012 0395plusmn0009 0355plusmn0086 0352plusmn0007 0340plusmn0004 0345plusmn0005 0302plusmn0004 0335plusmn0005 8
0385plusmn001 0380plusmn0010 0385plusmn00064 0380plusmn0008 0365plusmn0064 0367plusmn0004 0362plusmn0086 0372plusmn0106 0327plusmn0006 0362plusmn0016 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (6) Urine concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats
following repeated intramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)
Dose Time of a
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1125plusmn150 1125plusmn15 735plusmn287 81plusmn324 183plusmn03 555plusmn798 37plusmn0811 1815plusmn43290 -------------- ------ Before
2415plusmn357 2625plusmn374 1695plusmn788 249plusmn574 10575plusmn64 2415plusmn357 5400plusmn273 2085plusmn991 102plusmn160 168plusmn547 050
26025plusmn787 2923plusmn479 22425plusmn1225 2805plusmn35 1695plusmn618 2705plusmn471 10200plusmn547 2415plusmn357 6975plusmn225 22425plusmn894 1
29295plusmn765 3012plusmn346 28575plusmn738 2964plusmn415 2355plusmn259 2923plusmn479 1635plusmn561 2645plusmn917 102plusmn547 24825plusmn616 2
23475plusmn430 2482plusmn616 23475plusmn1564 2415plusmn357 1695plusmn788 198plusmn848 8475plusmn309 1515plusmn708 60plusmn212 1185plusmn45 4
1905plusmn45 2355plusmn259 153plusmn519 1935plusmn960 114plusmn948 159plusmn173 6675plusmn309 1215plusmn45 1312plusmn0552 855plusmn193 6
153plusmn1024 1965plusmn135 1335plusmn1229 150plusmn34 735plusmn295 1365plusmn665 6181plusmn339 72plusmn244 907plusmn0951 5025plusmn143 8
135plusmn519 120plusmn346 11725plusmn1551 96plusmn874 525plusmn295 75plusmn173 153plusmn130 39plusmn212 3735plusmn0458 13125plusmn0552 12
Between normal and diseased
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Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (7) Urineserum concentrations ratios of ceftriaxone following repeated ntramuscular injection of 20 mg
ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats
(n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
229plusmn 163 1448plusmn0743 1885plusmn159 1125plusmn0484 533plusmn0260 1050plusmn358 175plusmn0380 4146plusmn116 ------- ------ Before
741plusmn0063 plusmn01553 58plusmn0242 plusmn0149390 422plusmn0206 683plusmn0106 245plusmn0092 667plusmn0306 0510plusmn0081 559plusmn0181 050
651plusmn0243 plusmn0065031 637plusmn0373 plusmn014431 565plusmn0243 plusmn0085300 360plusmn0303 plusmn0110312 279plusmn0121 534plusmn0248 1
836plusmn0150 plusmn00476322 862plusmn0180 plusmn010463 942plusmn0166 plusmn0130631 217plusmn0303 727plusmn0256 508plusmn0186 plusmn01680340 2
939plusmn0235 plusmn01580344 1006plusmn0710 plusmn00750310 999plusmn0542 plusmn02850344 565plusmn0223 641plusmn0241 48plusmn0164 plusmn014834 4
1005plusmn0418 2plusmn018813 1097plusmn0641 plusmn03979300 993plusmn0921 plusmn0252931 619plusmn0483 plusmn0362933 167plusmn0101 642plusmn0644 6
1091plusmn0649 plusmn075332339 1171plusmn0980 995plusmn0415 925plusmn0593 plusmn05593433 886plusmn0408 plusmn02510311 2055plusmn0311 plusmn02046310 8
2392plusmn129 plusmn032731396 1794plusmn0228 1222plusmn124 1418plusmn109 plusmn026733336 580plusmn0397 plusmn03951326 227plusmn0452 plusmn02740316 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (8) Creatinine clearance (mlmin10kgbwt) following repeated intramuscular injection of 20 mg ceftriaxonekgbwt
twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats (n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1115plusmn0703 2265plusmn167 481plusmn0409 672plusmn0817 669plusmn0672 1202plusmn0777 695plusmn0634 1724plusmn179 ----------- ------ Before
0703plusmn0091 147plusmn0305 0718plusmn0141 251plusmn0707 0547plusmn0055 0699plusmn0092 0802plusmn0099 103plusmn0106 295plusmn0124 0458plusmn0037 050
101plusmn0075 161plusmn0093 131plusmn0099 264plusmn0217 161plusmn0146 373plusmn0499 247plusmn0110 4755plusmn0582 214plusmn0234 103plusmn0166 1
157plusmn0198 387plusmn0340 173plusmn0501 267plusmn0217 187plusmn0563 287plusmn0499 451plusmn0223 972plusmn105 263plusmn0399 169plusmn0454 2
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
184plusmn0095 346plusmn0444 173plusmn0501 436plusmn0599 383plusmn0299 682plusmn0584 328plusmn0253 119plusmn153 123plusmn0057 292plusmn0742 4
221plusmn0242 411plusmn0661 241plusmn0186 663plusmn0584 308plusmn0234 422plusmn0314 353plusmn0393 548plusmn0901 105plusmn0057 264plusmn0294 6
261plusmn0295 476plusmn0339 319plusmn0273 753plusmn0676 106plusmn0207 0773plusmn0049 228plusmn0175 456plusmn0340 206plusmn0160 404plusmn0419 8
310plusmn0218 409plusmn0434 3264plusmn0153 669plusmn0476 209plusmn0189 235plusmn0337 217plusmn0143 377plusmn0342 240plusmn0218 6055plusmn0176 12
Between normal and diseased
Plt 005 Plt001 Plt0001
Table (9) Ceftriaxone clearance (mlmin10kgbwt following repeated intramuscular injection of 20 mg ceftriaxone kgbwt
twice in normal and experimentally Salmonella typhimurim infected goats (n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1048plusmn121 0557plusmn684 895plusmn113 0547plusmn560 238plusmn0222 103plusmn 480 0668plusmn0157 0173plusmn216 -------- ----------- Before
156plusmn0251 43204plusmn3322 0936plusmn0162 43211plusmn3334 0473plusmn0037 43469plusmn43964 0300plusmn0028 43341plusmn080 0190plusmn0137 43400plusmn43642 050
166plusmn0079 43323plusmn3311 157plusmn0178 43419plusmn3301 137plusmn0115 43311plusmn33022 0883plusmn0054 43341plusmn 133 0616plusmn0153 43120plusmn3301 1
254plusmn0272 43361plusmn3391 222plusmn0093 4331plusmn3390 243plusmn0180 43209plusmn3309 183plusmn0149 43310plusmn2340 128plusmn0153 43312plusmn3390 2
181plusmn0136 43339plusmn3316 161plusmn0129 433plusmn3329 144plusmn0100 43412plusmn3349 0821plusmn0072 0063plusmn0977 0654plusmn0065 43400plusmn4306 4
160plusmn0177 43393plusmn336 152plusmn0200 43416plusmn331 135plusmn0118 4332plusmn3322 0897plusmn0052 43304plusmn3330 0212plusmn0022 43460plusmn43112 6
153plusmn0049 43291plusmn234 163plusmn0242 43346plusmn3300 0891plusmn0272 43306plusmn3310 108plusmn0071 43416plusmn04310 0229plusmn0046 43490plusmn43916 8
340plusmn0522 43214plusmn2341 249plusmn0150 43112plusmn3393 186plusmn0159 43320plusmn336 0773plusmn0094 43390plusmn 134 0264plusmn0043 43400plusmn 54369 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
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Table (10) Ceftriaxone clearancecreatinine clearance following repeated ntramuscular injection of 20 mg
ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats
(n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
0934plusmn0083 0305plusmn0013 183plusmn0116 0864plusmn0098 0358plusmn0018 0279plusmn0047 0099plusmn0020 0127plusmn0001 ------- ----------- Before
220plusmn0115 0819plusmn0044 131plusmn00414 0458plusmn0029 0876plusmn0063 126plusmn0068 0361plusmn0011 0813plusmn0031 0018plusmn0003 108plusmn0062 050
164plusmn0078 0818plusmn0029 118plusmn0068 0546plusmn0027 0858plusmn0052 0407plusmn0041 0331plusmn0009 0287plusmn0025 0324plusmn0011 0909plusmn0187 1
161plusmn0044 0488plusmn0005 232plusmn128 0329plusmn0027 169plusmn0464 0686plusmn0050 0409plusmn0020 0220plusmn0029 0512plusmn0077 266plusmn177 2
0933plusmn0024 0394plusmn0005 0948plusmn0062 0296plusmn0007 0381plusmn0027 0160plusmn0008 0235plusmn0014 0083plusmn0006 0528plusmn0028 0362plusmn0041 4
0726plusmn0018 0411plusmn0028 0639plusmn0066 0204plusmn0006 0446plusmn0034 0286plusmn0008 0238plusmn0019 0214plusmn0006 020plusmn0013 0382plusmn0028 6
0609plusmn0072 0425plusmn0036 0508plusmn0052 0192plusmn0009 0524plusmn0146 174plusmn0083 0477plusmn0015 0213plusmn00018 0109plusmn0185 0222plusmn0006 8
108plusmn0128 0496plusmn0012 0942plusmn0004 0265plusmn0030 0891plusmn0056 0706plusmn0103 0351plusmn0022 0354plusmn0018 0111plusmn0021 0098plusmn0018 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
DISCUSSION
In the present investigation intravenous injection of 20 mg ceftriaxonekgbwt in normal goats the drug showed high serum level
(92plusmn 0408 μgml) at 5 minutes post-injection then its concentration was decreased gradually till reached its minimum level (18
plusmn0816μgml) at 8hours post-injection
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In the present investigation the intravenous injection of 20 mg ceftriaxonekgbwt In normal
goats showed that the drug disposition best fitted a two-compartments- open model a
compartment of plasma and rapid equilibrating tissues and a deeper slower compartment
The obtained result is consistent with those reported for ceftriaxone in lactating goats[9]
lactating ewe[25]
domestic cat[15]
calves[26]
and patanwadi sheep[8]
Also this phenomenon is
in agreement with those reported for other cephalosporines as ceftazidime in a rabbit[27]
cefepime in dog and neonatal foals[28]
ewes[29]
ceftriaxone in goats[9]
cefipime in calves[30]
ceftiofur in cross-bred friesian cattle[31]
cefipime in calves[32]
ceftiofur in cows[33]
cefpirome
in cross-bred calves[3]
cefazidime in goats[35]
and cefquinome in sheep and goats[36]
cefipime
in chickens[37]
Ceftriaxone was distributed after intravenous injection with a distribution phase (α) equal to
656 per hour with a short distribution half ndash life [t05 (α)] equal to 0104 hour The shorter
distribution half-life of ceftriaxone in goats suggested the rapid distribution of the drug in
body tissue and fluid and that nearly similar to that recorded for ceftriaxone in lactating
goats(012 hour)[9]
for ceftriaxone in lactating ewes (0152 hour)[2]
and for ceftriaxone in
calves( 013hour)[26]
The rapid distribution of ceftriaxone in goats is supported by high rate constant of transfer of
the drug from central to peripheral compartment [K12 = 353 h-1
] as compared to the rate
constant of transfer of the drug from peripheral to central compartment [K21= 295 h-1
] This
value is nearly similar to those reported for cefotaxime in goats (K21=327 h-1
)[38]
On contrast
this value was higher than those recorded for ceftriaxone in lactating goats (K21=143 h-1
)[9]
in
lactating ewes (K21=125 h-1
)[25]
and in domestic cats (K21=154 h-1
)[15]
The apparent volume of distribution of ceftriaxone was (0355plusmn0004LKg) this value is
nearly similar to that recorded for cefaronide in sheep(039 LKg)[7]
cefotaxime in dog (048
lkg)[39]
in goat (051 lkg)
[40] for caphalexin in buffalo calves (041 Lkg)
[41] for cefipime in
ewes and calves (032 lkg) (043Lkg)[29]
and[30]
respectively For ceftriaxone in domestic
cats (057Lkg)[15]
in camel (032Lkg)[42]
On the other hand this result is differ than that
reported for cefotaxime in buffalo calves (117Lkg)[43]
High value of the volume of
distribution suggested extensive penetration power Drug with volume of distribution greater
than one literkilogram indicated wide distribution or extensive tissue binding or both[44]
The
apparent volume of distribution in the present study indicated moderate tissue penetrating
power This result agreed with[15]
for ceftriaxone in domestic cats
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
Ceftriaxone is eliminated in the current study following a single intravenous injection with
elimination half ndashlife [t 05(β)] equal to 519 hours This observation is nearly agreed with the
data recorded for ceftizoxime in goats (624hours)[45]
On contrast this value was longer than
that reported for ceftriaxone in lactating ewe (175hours)[25]
for cefaronide in sheep (17
hours)[7]
For cephalexin in buffulo calves (216hours)[41]
for ceftriaxone in healthy horse
(162hours)[46]
also this value is longer than that recorded for ceftriaxone in lactating goats
(144hours)[9]
for cefipime in goats (186hours)[47]
The rate of total body clearance of ceftriaxone following a single intravenous injection is
0048 lkgh which equal to data reported for ceftizoxime in lactating goats (005Lkgh)[45]
On contrast this value is lower than that reported for ceftriaxone in buffulo calves lactating
goats buffulo calves (Bubalus bubalis) goats (capra hircus) patanwadi sheep (026 Lkgh)
(395 Lkgh) (440 Lkgh) (450 Lkgh) (391 Lkgh)[12913118]
respectively
The variation in total body clearance might be attributed to specific interspecies variation
handling of the drug method used healthy status of the animal[48]
The difference between values calculated for pharmacokinetic parameters may be attributed
to animal species the drug formulation employed the age the size or sex o l lf the animal
or even inter individual variation and also due to method of analysis of the drug[49]
Following a single intramuscular injection of 20 mg ceftriaxonekg bwt In normal goats the
drug reached its peak serum concentrations after one hour of injection with value
of(41μgml) Ceftriaxone could be detected in serum in a therapeutic level (263μgml) at 12
hours post-injection The reported peak serum concentrations neerly similar to that reported
for cephalexin in buffulo calves (457 microgml)[41]
These results is differed than those reported
for ceftriaxone in cross breed calves (188 microgml at 30 min[16]
in Kangro breed of goats
(Capra Hircus) (2640 microgml at 20 min[10][50]
found after intramuscular administration of
ceforazone peak plasma concentration was (976 microgml) at 45min This result was also higher
than that recorded for ceftriaxone in buffalo calves (158 microgml)[13]
The calculated maximum serum concentration (Cmax) is (40015 microgml) at maximum time
(tmax) of 157 hours The reported (Cmax) agreed with the data reported for cefipime in goats
(4932 microgml[47]
The reported maximum serum concentration (Cmax) is higher than that
reported for ceftriaxone in lactating goats(236 microgml)[9]
in lactating ewes (1722 microgml[25]
in
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
goats (2151 microgml)[11]
for cefquinome in camels (123 microgml)[51]
for ceftriaxone in calves
(1534 microgml)[26]
in patanwadi sheep (1553 microgml)[8]
for cefpirome in cattle (101 microgml)[52]
And for ceftiofur in chickens (2594 μgml)[37]
On the other hand the result was lower than
that reported by[6]
who observed the maximum serum concentration (Cmax) of ceftriaxone in
human after ntramuscular administration was (805 microgml) also it was lower than that
reported for ceftriaxone in dog (11510 microgml)[53]
in domestic cats (5440 microgml)[15]
and for
ceftazoxime in goats (8878 microgml)[45]
The reported [tmax] is neerly similar to that reported for ceftriaxone (104hours)in lactating
ewes by[25]
On contrast it is longer than those reported for ceftriaxone in dogs
(129hours)[53]
for ceftriaxone in lactating goats (07hours)[9]
also the result was longer than
that reported for ceftriaxone in domestic cats (033hours)[15]
in buffulo calves (05 hours)[13]
and for cefpirome in cattle (075hours)[52]
The reported [tmax] is shorter than those reported
for cefquinome in camels (425hours)[51]
in sheep and goats (261 and 262 hours)[36]
and for
ceftiofur in chickens (251 hours)[37]
The elimination half life [t05(β)]
following a single intramuscular administration was 1804 hours This value is nearly agreed
with that recorded for cefquinomein camels (1024hours)[52]
On contrast this result is longer
than that reported for cephalexin in buffalo calves (243hours)[41]
for ceftriaxone in lactating
ewes (177hours)[25]
in buffalo calves (438hours)[13]
in goats (203 hours)[11]
and for
cefipime in goats (165 hours)[47]
The rate of total body clearance of ceftriaxone following a single intramuscular injection is
0043lkgh This value was lower than that reported for ceftriaxone in buffulo calves
(401Lkgh)[13]
in goats (304 Lkgh)[11]
and in sheep (222 Lkgh)[8]
Bioavailability is the fraction of the drug administered by non vascular rout that gains
accesses to the systemic circulation The obtained result revealed that the calculated systemic
bioavailability percent was 6128 It is equal to that recorded for cefpirome in cow calves
(61)[54]
It is nearly equal to that recorded for ceftriaxone in sheep (64)[8]
On the other
hand this value is higher than those recorded for cefperazone in crossbred calves (481)[50]
for ceftriaxone in goats (59)[11]
in calves (47)[55]
On contrast this value is lower than
those reported for cefotaxime in two cats 982 and 93)[57]
for cephradine in goats
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
(739)[58]
for ceftazidime in a rabbit (966)[27]
for ceftriaxone in lactating goats (85)[9]
in lactating ewes (836)[25]
in domestic cats 8572[15]
for cefipime in goats 8645[47]
for ceftriaxone in buffulo calves 702[13]
and for ceftiofur in chickens 8890[37]
Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium
infected goats twics dialy for five days revealed that the drug could be detected in a
therapeutic level for 12hours following repeated intramuscular administrations and exceeded
the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]
The relative higher serum concentrations of ceftriaxone after the last dose compared to the
first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12
hours intervals for five consecutive days These observations agreed with data reported by[36]
on comparing the data of serum levels of repeated intramuscular injections with first
intramuscular injection it was revealed that repeated intramuscular injections of cefquinome
have cumulative effect in both species sheep and goats
The obtained result is inconsistent with that reported by[56]
who found thatwhen cefotaxime
was administered repetitively in patients the ratio of maximal serum levels after the last dose
to those after the first dose demonstrated minimal accumulation of intact drug and by[60]
who
found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in
buffalo calves
The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium
infected goats are significantly lower than those in normal goats following repeated
intramuscular injection These lower blood concentrations in Salmonella typhimurium
infected goats might be attributed to the higher penetrating power of ceftriaxone to the
diseased tissues[48]
This phenomenon is similar to data recorded by[61]
who suggested that
Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of
ceftriaxone These alterations might be due to fever and inflammation induced by
infections[59]
proved that the serum concentrations of cephradine following intramuscular
administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after
each intramuscular dose with a lower significant values recorded in Escherichia-coli infected
goats than in normal goatsAlso similer to that reported by[62]
who observed that the
maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep
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1451
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
in comparison to normal sheepOn contrast[43]
reported that peak plasma level of cefotaxime
in febrile buffalo calves was higher than healthy buffalo calves
In this study the total body clearance (CLtot) in normal goats are significantly lower than in
Salmonella typhimurium infected goats This result supported by[61]
and[63]
fever and
inflammation are cardinal features in bacterial infection which may in turn caused an
increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all
these could lead to increased in the rate at which the drug was delivered to both organs which
were important sites of drug excretion This might somewhat explain the increase in the total
body clearance in infected goats This result is differ than that reported by[64]
who observed
that the clearance of ceftriaxone was significantly reduced in infected mice than in non
infected animals
The highest concentrations of ceftriaxone in milk are recorded 4 hours after each
intramuscular injection with a significant lower value in Salmonella typhimurium infected
goats than in normal goats This might be attributed to accumulation of drug in the inflammed
tissues[48]
This result is similar to those reported by[6559]
who found that milk concentrations
of gentamicin and cephradine were significantly lower in infected goats and cattle than in
normal ones respectively
The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the
non-ionic passive diffusion principle[66]
reported that most drug cross-lipid membranes by
passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly
influenced by the physicochemical properties of the drug[6768]
Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum
ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the
physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]
Milk
contains substantially more lipid and less protein than serum and is slightly more acidic
Therefore drugs which tend to concentrated in milk are weak bases with low serum protein
binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide
and aminothiazole also possesses an hydroxytriazinone group as new and additional
ionization center[70]
these compounds are sufficiently lipid- soluble to be able to penetrate
tissues
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
The dose of ceftriaxone used in the present study induced therapeutically concentrations in
milk These concentrations suggested that ceftriaxone would be efficacious in treatment of
mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily
for 3-5 days
The study showed that the urine concentrations of ceftriaxone are greater than the concurrent
serum concentrations following intramuscular injection This observation is similar to those
reported in cows after cephapirin administrations[71]
In the present study urine concentrations of ceftriaxone increased with the repetition of
dosing This observation supported by[72]
after repeated intramuscular administrations of
ceftriaxone in healthy volunteeres
The mean peak urine concentrations of ceftriaxone were reached 2 hours after each
intramuscular injection The lower urine ceftriaxone concentrations in Salmonella
typhimurium infected goats than in normal goats might be attributed to the accumulation of
the drug in the inflamed tissues[48]
The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower
ratio in Salmonella typhimurium infected goats than in normal goats at different time of
sampling This indicates that glomerular filteration seemed to be the main pathway of
ceftriaxone elimination This observation supported by[59]
who found that the ratio between
cephradine clearance from blood of goats to creatinine clearance showed a marked decrease
in Escherichia-coli infected goats than in normal goats This indicated that glomerular
filteration seemed to be the main pathway of cephradine elimination with a limited rate of
tubular reabsorption
CONCLUSION
The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value
referred a better absorption of ceftriaxone from its site of intramuscular administration The
high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular
administrations suggested that ceftriaxone could be used for treatment of mastitis caused by
Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats
The high concentrations of ceftriaxone in urine after repeated intramuscular administrations
suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections
wwwwjppscom Vol 5 Issue 01 2016
1453
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in
goats
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Table (5) The amount of urine (mlmin) voided in normal and experimentally Salmonella typhimurim infected goats following
repeated intramuscular injection of 20 mg ceftriaxonekgbwt twice dialy for five consecutive days (n=4)
Dose Time of a
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
plusmn00372344 126plusmn0034 130plusmn0030 130plusmn0028 118plusmn0066 118plusmn0067 108plusmn0013 108plusmn0008 ----------- -------- Before
0577plusmn0069 43494057plusmn 045plusmn0060 plusmn0064309 0312plusmn002 033plusmn0012 0340plusmn0024 033plusmn0012 0287plusmn0017 0272plusmn0014 050
0712plusmn0019 0692plusmn0014 068plusmn0081 0697plusmn0006 0672plusmn0011 0675plusmn 0009 0635plusmn0032 0655plusmn0010 0719plusmn0031 0697plusmn0015 1
0837plusmn0025 0787plusmn0021 0732plusmn0011 plusmn00054300 0715plusmn0011 0715plusmn002 0722plusmn0019 0702plusmn0018 0737plusmn0027 0762plusmn0041 2
0535plusmn0095 0507plusmn0021 0447plusmn0022 0452plusmn002 0402plusmn0075 0405plusmn0011 0400plusmn0057 0397plusmn0009 0380plusmn0004 038plusmn001 4
0437plusmn00094 0432plusmn0008 0400plusmn0010 0405plusmn0002 0380plusmn0007 plusmn00044319 0372plusmn0047 037plusmn 0007 0350plusmn0005 0365plusmn0006 6
0397plusmn0028 0410plusmn0008 0380plusmn0012 0395plusmn0009 0355plusmn0086 0352plusmn0007 0340plusmn0004 0345plusmn0005 0302plusmn0004 0335plusmn0005 8
0385plusmn001 0380plusmn0010 0385plusmn00064 0380plusmn0008 0365plusmn0064 0367plusmn0004 0362plusmn0086 0372plusmn0106 0327plusmn0006 0362plusmn0016 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (6) Urine concentrations of ceftriaxone (microgml) in normal and experimentally Salmonella typhimurim infected goats
following repeated intramuscular injection of 20 mg ceftriaxone kgbwt twice dialy for five consecutive days (n=4)
Dose Time of a
administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1125plusmn150 1125plusmn15 735plusmn287 81plusmn324 183plusmn03 555plusmn798 37plusmn0811 1815plusmn43290 -------------- ------ Before
2415plusmn357 2625plusmn374 1695plusmn788 249plusmn574 10575plusmn64 2415plusmn357 5400plusmn273 2085plusmn991 102plusmn160 168plusmn547 050
26025plusmn787 2923plusmn479 22425plusmn1225 2805plusmn35 1695plusmn618 2705plusmn471 10200plusmn547 2415plusmn357 6975plusmn225 22425plusmn894 1
29295plusmn765 3012plusmn346 28575plusmn738 2964plusmn415 2355plusmn259 2923plusmn479 1635plusmn561 2645plusmn917 102plusmn547 24825plusmn616 2
23475plusmn430 2482plusmn616 23475plusmn1564 2415plusmn357 1695plusmn788 198plusmn848 8475plusmn309 1515plusmn708 60plusmn212 1185plusmn45 4
1905plusmn45 2355plusmn259 153plusmn519 1935plusmn960 114plusmn948 159plusmn173 6675plusmn309 1215plusmn45 1312plusmn0552 855plusmn193 6
153plusmn1024 1965plusmn135 1335plusmn1229 150plusmn34 735plusmn295 1365plusmn665 6181plusmn339 72plusmn244 907plusmn0951 5025plusmn143 8
135plusmn519 120plusmn346 11725plusmn1551 96plusmn874 525plusmn295 75plusmn173 153plusmn130 39plusmn212 3735plusmn0458 13125plusmn0552 12
Between normal and diseased
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (7) Urineserum concentrations ratios of ceftriaxone following repeated ntramuscular injection of 20 mg
ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats
(n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
229plusmn 163 1448plusmn0743 1885plusmn159 1125plusmn0484 533plusmn0260 1050plusmn358 175plusmn0380 4146plusmn116 ------- ------ Before
741plusmn0063 plusmn01553 58plusmn0242 plusmn0149390 422plusmn0206 683plusmn0106 245plusmn0092 667plusmn0306 0510plusmn0081 559plusmn0181 050
651plusmn0243 plusmn0065031 637plusmn0373 plusmn014431 565plusmn0243 plusmn0085300 360plusmn0303 plusmn0110312 279plusmn0121 534plusmn0248 1
836plusmn0150 plusmn00476322 862plusmn0180 plusmn010463 942plusmn0166 plusmn0130631 217plusmn0303 727plusmn0256 508plusmn0186 plusmn01680340 2
939plusmn0235 plusmn01580344 1006plusmn0710 plusmn00750310 999plusmn0542 plusmn02850344 565plusmn0223 641plusmn0241 48plusmn0164 plusmn014834 4
1005plusmn0418 2plusmn018813 1097plusmn0641 plusmn03979300 993plusmn0921 plusmn0252931 619plusmn0483 plusmn0362933 167plusmn0101 642plusmn0644 6
1091plusmn0649 plusmn075332339 1171plusmn0980 995plusmn0415 925plusmn0593 plusmn05593433 886plusmn0408 plusmn02510311 2055plusmn0311 plusmn02046310 8
2392plusmn129 plusmn032731396 1794plusmn0228 1222plusmn124 1418plusmn109 plusmn026733336 580plusmn0397 plusmn03951326 227plusmn0452 plusmn02740316 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (8) Creatinine clearance (mlmin10kgbwt) following repeated intramuscular injection of 20 mg ceftriaxonekgbwt
twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats (n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1115plusmn0703 2265plusmn167 481plusmn0409 672plusmn0817 669plusmn0672 1202plusmn0777 695plusmn0634 1724plusmn179 ----------- ------ Before
0703plusmn0091 147plusmn0305 0718plusmn0141 251plusmn0707 0547plusmn0055 0699plusmn0092 0802plusmn0099 103plusmn0106 295plusmn0124 0458plusmn0037 050
101plusmn0075 161plusmn0093 131plusmn0099 264plusmn0217 161plusmn0146 373plusmn0499 247plusmn0110 4755plusmn0582 214plusmn0234 103plusmn0166 1
157plusmn0198 387plusmn0340 173plusmn0501 267plusmn0217 187plusmn0563 287plusmn0499 451plusmn0223 972plusmn105 263plusmn0399 169plusmn0454 2
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
184plusmn0095 346plusmn0444 173plusmn0501 436plusmn0599 383plusmn0299 682plusmn0584 328plusmn0253 119plusmn153 123plusmn0057 292plusmn0742 4
221plusmn0242 411plusmn0661 241plusmn0186 663plusmn0584 308plusmn0234 422plusmn0314 353plusmn0393 548plusmn0901 105plusmn0057 264plusmn0294 6
261plusmn0295 476plusmn0339 319plusmn0273 753plusmn0676 106plusmn0207 0773plusmn0049 228plusmn0175 456plusmn0340 206plusmn0160 404plusmn0419 8
310plusmn0218 409plusmn0434 3264plusmn0153 669plusmn0476 209plusmn0189 235plusmn0337 217plusmn0143 377plusmn0342 240plusmn0218 6055plusmn0176 12
Between normal and diseased
Plt 005 Plt001 Plt0001
Table (9) Ceftriaxone clearance (mlmin10kgbwt following repeated intramuscular injection of 20 mg ceftriaxone kgbwt
twice in normal and experimentally Salmonella typhimurim infected goats (n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1048plusmn121 0557plusmn684 895plusmn113 0547plusmn560 238plusmn0222 103plusmn 480 0668plusmn0157 0173plusmn216 -------- ----------- Before
156plusmn0251 43204plusmn3322 0936plusmn0162 43211plusmn3334 0473plusmn0037 43469plusmn43964 0300plusmn0028 43341plusmn080 0190plusmn0137 43400plusmn43642 050
166plusmn0079 43323plusmn3311 157plusmn0178 43419plusmn3301 137plusmn0115 43311plusmn33022 0883plusmn0054 43341plusmn 133 0616plusmn0153 43120plusmn3301 1
254plusmn0272 43361plusmn3391 222plusmn0093 4331plusmn3390 243plusmn0180 43209plusmn3309 183plusmn0149 43310plusmn2340 128plusmn0153 43312plusmn3390 2
181plusmn0136 43339plusmn3316 161plusmn0129 433plusmn3329 144plusmn0100 43412plusmn3349 0821plusmn0072 0063plusmn0977 0654plusmn0065 43400plusmn4306 4
160plusmn0177 43393plusmn336 152plusmn0200 43416plusmn331 135plusmn0118 4332plusmn3322 0897plusmn0052 43304plusmn3330 0212plusmn0022 43460plusmn43112 6
153plusmn0049 43291plusmn234 163plusmn0242 43346plusmn3300 0891plusmn0272 43306plusmn3310 108plusmn0071 43416plusmn04310 0229plusmn0046 43490plusmn43916 8
340plusmn0522 43214plusmn2341 249plusmn0150 43112plusmn3393 186plusmn0159 43320plusmn336 0773plusmn0094 43390plusmn 134 0264plusmn0043 43400plusmn 54369 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
Table (10) Ceftriaxone clearancecreatinine clearance following repeated ntramuscular injection of 20 mg
ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats
(n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
0934plusmn0083 0305plusmn0013 183plusmn0116 0864plusmn0098 0358plusmn0018 0279plusmn0047 0099plusmn0020 0127plusmn0001 ------- ----------- Before
220plusmn0115 0819plusmn0044 131plusmn00414 0458plusmn0029 0876plusmn0063 126plusmn0068 0361plusmn0011 0813plusmn0031 0018plusmn0003 108plusmn0062 050
164plusmn0078 0818plusmn0029 118plusmn0068 0546plusmn0027 0858plusmn0052 0407plusmn0041 0331plusmn0009 0287plusmn0025 0324plusmn0011 0909plusmn0187 1
161plusmn0044 0488plusmn0005 232plusmn128 0329plusmn0027 169plusmn0464 0686plusmn0050 0409plusmn0020 0220plusmn0029 0512plusmn0077 266plusmn177 2
0933plusmn0024 0394plusmn0005 0948plusmn0062 0296plusmn0007 0381plusmn0027 0160plusmn0008 0235plusmn0014 0083plusmn0006 0528plusmn0028 0362plusmn0041 4
0726plusmn0018 0411plusmn0028 0639plusmn0066 0204plusmn0006 0446plusmn0034 0286plusmn0008 0238plusmn0019 0214plusmn0006 020plusmn0013 0382plusmn0028 6
0609plusmn0072 0425plusmn0036 0508plusmn0052 0192plusmn0009 0524plusmn0146 174plusmn0083 0477plusmn0015 0213plusmn00018 0109plusmn0185 0222plusmn0006 8
108plusmn0128 0496plusmn0012 0942plusmn0004 0265plusmn0030 0891plusmn0056 0706plusmn0103 0351plusmn0022 0354plusmn0018 0111plusmn0021 0098plusmn0018 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
DISCUSSION
In the present investigation intravenous injection of 20 mg ceftriaxonekgbwt in normal goats the drug showed high serum level
(92plusmn 0408 μgml) at 5 minutes post-injection then its concentration was decreased gradually till reached its minimum level (18
plusmn0816μgml) at 8hours post-injection
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
In the present investigation the intravenous injection of 20 mg ceftriaxonekgbwt In normal
goats showed that the drug disposition best fitted a two-compartments- open model a
compartment of plasma and rapid equilibrating tissues and a deeper slower compartment
The obtained result is consistent with those reported for ceftriaxone in lactating goats[9]
lactating ewe[25]
domestic cat[15]
calves[26]
and patanwadi sheep[8]
Also this phenomenon is
in agreement with those reported for other cephalosporines as ceftazidime in a rabbit[27]
cefepime in dog and neonatal foals[28]
ewes[29]
ceftriaxone in goats[9]
cefipime in calves[30]
ceftiofur in cross-bred friesian cattle[31]
cefipime in calves[32]
ceftiofur in cows[33]
cefpirome
in cross-bred calves[3]
cefazidime in goats[35]
and cefquinome in sheep and goats[36]
cefipime
in chickens[37]
Ceftriaxone was distributed after intravenous injection with a distribution phase (α) equal to
656 per hour with a short distribution half ndash life [t05 (α)] equal to 0104 hour The shorter
distribution half-life of ceftriaxone in goats suggested the rapid distribution of the drug in
body tissue and fluid and that nearly similar to that recorded for ceftriaxone in lactating
goats(012 hour)[9]
for ceftriaxone in lactating ewes (0152 hour)[2]
and for ceftriaxone in
calves( 013hour)[26]
The rapid distribution of ceftriaxone in goats is supported by high rate constant of transfer of
the drug from central to peripheral compartment [K12 = 353 h-1
] as compared to the rate
constant of transfer of the drug from peripheral to central compartment [K21= 295 h-1
] This
value is nearly similar to those reported for cefotaxime in goats (K21=327 h-1
)[38]
On contrast
this value was higher than those recorded for ceftriaxone in lactating goats (K21=143 h-1
)[9]
in
lactating ewes (K21=125 h-1
)[25]
and in domestic cats (K21=154 h-1
)[15]
The apparent volume of distribution of ceftriaxone was (0355plusmn0004LKg) this value is
nearly similar to that recorded for cefaronide in sheep(039 LKg)[7]
cefotaxime in dog (048
lkg)[39]
in goat (051 lkg)
[40] for caphalexin in buffalo calves (041 Lkg)
[41] for cefipime in
ewes and calves (032 lkg) (043Lkg)[29]
and[30]
respectively For ceftriaxone in domestic
cats (057Lkg)[15]
in camel (032Lkg)[42]
On the other hand this result is differ than that
reported for cefotaxime in buffalo calves (117Lkg)[43]
High value of the volume of
distribution suggested extensive penetration power Drug with volume of distribution greater
than one literkilogram indicated wide distribution or extensive tissue binding or both[44]
The
apparent volume of distribution in the present study indicated moderate tissue penetrating
power This result agreed with[15]
for ceftriaxone in domestic cats
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
Ceftriaxone is eliminated in the current study following a single intravenous injection with
elimination half ndashlife [t 05(β)] equal to 519 hours This observation is nearly agreed with the
data recorded for ceftizoxime in goats (624hours)[45]
On contrast this value was longer than
that reported for ceftriaxone in lactating ewe (175hours)[25]
for cefaronide in sheep (17
hours)[7]
For cephalexin in buffulo calves (216hours)[41]
for ceftriaxone in healthy horse
(162hours)[46]
also this value is longer than that recorded for ceftriaxone in lactating goats
(144hours)[9]
for cefipime in goats (186hours)[47]
The rate of total body clearance of ceftriaxone following a single intravenous injection is
0048 lkgh which equal to data reported for ceftizoxime in lactating goats (005Lkgh)[45]
On contrast this value is lower than that reported for ceftriaxone in buffulo calves lactating
goats buffulo calves (Bubalus bubalis) goats (capra hircus) patanwadi sheep (026 Lkgh)
(395 Lkgh) (440 Lkgh) (450 Lkgh) (391 Lkgh)[12913118]
respectively
The variation in total body clearance might be attributed to specific interspecies variation
handling of the drug method used healthy status of the animal[48]
The difference between values calculated for pharmacokinetic parameters may be attributed
to animal species the drug formulation employed the age the size or sex o l lf the animal
or even inter individual variation and also due to method of analysis of the drug[49]
Following a single intramuscular injection of 20 mg ceftriaxonekg bwt In normal goats the
drug reached its peak serum concentrations after one hour of injection with value
of(41μgml) Ceftriaxone could be detected in serum in a therapeutic level (263μgml) at 12
hours post-injection The reported peak serum concentrations neerly similar to that reported
for cephalexin in buffulo calves (457 microgml)[41]
These results is differed than those reported
for ceftriaxone in cross breed calves (188 microgml at 30 min[16]
in Kangro breed of goats
(Capra Hircus) (2640 microgml at 20 min[10][50]
found after intramuscular administration of
ceforazone peak plasma concentration was (976 microgml) at 45min This result was also higher
than that recorded for ceftriaxone in buffalo calves (158 microgml)[13]
The calculated maximum serum concentration (Cmax) is (40015 microgml) at maximum time
(tmax) of 157 hours The reported (Cmax) agreed with the data reported for cefipime in goats
(4932 microgml[47]
The reported maximum serum concentration (Cmax) is higher than that
reported for ceftriaxone in lactating goats(236 microgml)[9]
in lactating ewes (1722 microgml[25]
in
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
goats (2151 microgml)[11]
for cefquinome in camels (123 microgml)[51]
for ceftriaxone in calves
(1534 microgml)[26]
in patanwadi sheep (1553 microgml)[8]
for cefpirome in cattle (101 microgml)[52]
And for ceftiofur in chickens (2594 μgml)[37]
On the other hand the result was lower than
that reported by[6]
who observed the maximum serum concentration (Cmax) of ceftriaxone in
human after ntramuscular administration was (805 microgml) also it was lower than that
reported for ceftriaxone in dog (11510 microgml)[53]
in domestic cats (5440 microgml)[15]
and for
ceftazoxime in goats (8878 microgml)[45]
The reported [tmax] is neerly similar to that reported for ceftriaxone (104hours)in lactating
ewes by[25]
On contrast it is longer than those reported for ceftriaxone in dogs
(129hours)[53]
for ceftriaxone in lactating goats (07hours)[9]
also the result was longer than
that reported for ceftriaxone in domestic cats (033hours)[15]
in buffulo calves (05 hours)[13]
and for cefpirome in cattle (075hours)[52]
The reported [tmax] is shorter than those reported
for cefquinome in camels (425hours)[51]
in sheep and goats (261 and 262 hours)[36]
and for
ceftiofur in chickens (251 hours)[37]
The elimination half life [t05(β)]
following a single intramuscular administration was 1804 hours This value is nearly agreed
with that recorded for cefquinomein camels (1024hours)[52]
On contrast this result is longer
than that reported for cephalexin in buffalo calves (243hours)[41]
for ceftriaxone in lactating
ewes (177hours)[25]
in buffalo calves (438hours)[13]
in goats (203 hours)[11]
and for
cefipime in goats (165 hours)[47]
The rate of total body clearance of ceftriaxone following a single intramuscular injection is
0043lkgh This value was lower than that reported for ceftriaxone in buffulo calves
(401Lkgh)[13]
in goats (304 Lkgh)[11]
and in sheep (222 Lkgh)[8]
Bioavailability is the fraction of the drug administered by non vascular rout that gains
accesses to the systemic circulation The obtained result revealed that the calculated systemic
bioavailability percent was 6128 It is equal to that recorded for cefpirome in cow calves
(61)[54]
It is nearly equal to that recorded for ceftriaxone in sheep (64)[8]
On the other
hand this value is higher than those recorded for cefperazone in crossbred calves (481)[50]
for ceftriaxone in goats (59)[11]
in calves (47)[55]
On contrast this value is lower than
those reported for cefotaxime in two cats 982 and 93)[57]
for cephradine in goats
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
(739)[58]
for ceftazidime in a rabbit (966)[27]
for ceftriaxone in lactating goats (85)[9]
in lactating ewes (836)[25]
in domestic cats 8572[15]
for cefipime in goats 8645[47]
for ceftriaxone in buffulo calves 702[13]
and for ceftiofur in chickens 8890[37]
Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium
infected goats twics dialy for five days revealed that the drug could be detected in a
therapeutic level for 12hours following repeated intramuscular administrations and exceeded
the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]
The relative higher serum concentrations of ceftriaxone after the last dose compared to the
first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12
hours intervals for five consecutive days These observations agreed with data reported by[36]
on comparing the data of serum levels of repeated intramuscular injections with first
intramuscular injection it was revealed that repeated intramuscular injections of cefquinome
have cumulative effect in both species sheep and goats
The obtained result is inconsistent with that reported by[56]
who found thatwhen cefotaxime
was administered repetitively in patients the ratio of maximal serum levels after the last dose
to those after the first dose demonstrated minimal accumulation of intact drug and by[60]
who
found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in
buffalo calves
The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium
infected goats are significantly lower than those in normal goats following repeated
intramuscular injection These lower blood concentrations in Salmonella typhimurium
infected goats might be attributed to the higher penetrating power of ceftriaxone to the
diseased tissues[48]
This phenomenon is similar to data recorded by[61]
who suggested that
Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of
ceftriaxone These alterations might be due to fever and inflammation induced by
infections[59]
proved that the serum concentrations of cephradine following intramuscular
administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after
each intramuscular dose with a lower significant values recorded in Escherichia-coli infected
goats than in normal goatsAlso similer to that reported by[62]
who observed that the
maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
in comparison to normal sheepOn contrast[43]
reported that peak plasma level of cefotaxime
in febrile buffalo calves was higher than healthy buffalo calves
In this study the total body clearance (CLtot) in normal goats are significantly lower than in
Salmonella typhimurium infected goats This result supported by[61]
and[63]
fever and
inflammation are cardinal features in bacterial infection which may in turn caused an
increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all
these could lead to increased in the rate at which the drug was delivered to both organs which
were important sites of drug excretion This might somewhat explain the increase in the total
body clearance in infected goats This result is differ than that reported by[64]
who observed
that the clearance of ceftriaxone was significantly reduced in infected mice than in non
infected animals
The highest concentrations of ceftriaxone in milk are recorded 4 hours after each
intramuscular injection with a significant lower value in Salmonella typhimurium infected
goats than in normal goats This might be attributed to accumulation of drug in the inflammed
tissues[48]
This result is similar to those reported by[6559]
who found that milk concentrations
of gentamicin and cephradine were significantly lower in infected goats and cattle than in
normal ones respectively
The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the
non-ionic passive diffusion principle[66]
reported that most drug cross-lipid membranes by
passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly
influenced by the physicochemical properties of the drug[6768]
Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum
ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the
physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]
Milk
contains substantially more lipid and less protein than serum and is slightly more acidic
Therefore drugs which tend to concentrated in milk are weak bases with low serum protein
binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide
and aminothiazole also possesses an hydroxytriazinone group as new and additional
ionization center[70]
these compounds are sufficiently lipid- soluble to be able to penetrate
tissues
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The dose of ceftriaxone used in the present study induced therapeutically concentrations in
milk These concentrations suggested that ceftriaxone would be efficacious in treatment of
mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily
for 3-5 days
The study showed that the urine concentrations of ceftriaxone are greater than the concurrent
serum concentrations following intramuscular injection This observation is similar to those
reported in cows after cephapirin administrations[71]
In the present study urine concentrations of ceftriaxone increased with the repetition of
dosing This observation supported by[72]
after repeated intramuscular administrations of
ceftriaxone in healthy volunteeres
The mean peak urine concentrations of ceftriaxone were reached 2 hours after each
intramuscular injection The lower urine ceftriaxone concentrations in Salmonella
typhimurium infected goats than in normal goats might be attributed to the accumulation of
the drug in the inflamed tissues[48]
The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower
ratio in Salmonella typhimurium infected goats than in normal goats at different time of
sampling This indicates that glomerular filteration seemed to be the main pathway of
ceftriaxone elimination This observation supported by[59]
who found that the ratio between
cephradine clearance from blood of goats to creatinine clearance showed a marked decrease
in Escherichia-coli infected goats than in normal goats This indicated that glomerular
filteration seemed to be the main pathway of cephradine elimination with a limited rate of
tubular reabsorption
CONCLUSION
The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value
referred a better absorption of ceftriaxone from its site of intramuscular administration The
high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular
administrations suggested that ceftriaxone could be used for treatment of mastitis caused by
Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats
The high concentrations of ceftriaxone in urine after repeated intramuscular administrations
suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections
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caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in
goats
REFERANCES
1 Neu HC Merpol NJ and Fukp (1981) Antibacterial activity of ceftriaxone
abetalactamase stable cephalosporines Antimicrobial agents and chemotherapy 19
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25 Goudah A Shin HC Shim JH Abd El-Aty AM (2006) Characterization of the
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27 Abd-El-Aty AM Goudah A and Abo E S K (2001) Pharmacokinetics
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28 Gardner S Y and Papich M G (2001) Comparison of cefepime pharmacokinetics in
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30 Patel U D Bhavsar S K and Thaker A M (2006) Pharmacokinetics and dosage
regimen of cefepime following single dose intravenous administration in calves Iran J
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31 El-Gendy AAM Tohamy MA and Ismail M (2007) Comparative pharmacokinetic
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32 Joshi B and Kumar Sharma S (2009) The pharmacokinetics of cefepime in E coli
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33 Tohamy MA (2008) Pharmacokinetics of ceftiofur sodium administered concomitantly
with dipyrone in healthy and feverish cows J Egypt Soc Pharmacol Exp Ther 29(2)
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34 Rajput N Kumar V D and Sandhu HS (2011) Pharmacokinetics and dosage
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35 Abo-El- Sooud K and Tohamy MA (2011) Comparative pharmacokinetics and milk
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administrations in sheep and goats J Vet Med Doi 949642 1-5
37 El-Sayed M G A El-Komy A A A El barawy A M and Ibrahim D M A (2015)
Pharmacokinetics and tissue residues of ceftiofur in normal and Escherichia coli infected
chickens J Phys Pharm Adv 5(3) 574-582
38 Datta B Mandal TK and Chakraborty A K (2003) Pharmacokinetics of cefotaxime
in goats with experimentally induced kidney damage Ind J pharmacol (35) 173-176
39 Guerrini HV English BP Filippich J L Schneider J and Bourne D W (1986)
The pharmacokinetics of cefotaxime in dog Vet Rec 119(4) 81-83
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40 Atef M Ramadan A Afifi N A and Youssef S A (1990) pharmacokinetic profile
of cefotaxime in goat Res Vet Sci 49(1) 34-38
41 Satish K G Chaudhary RK Srivastiva AK and Garg BD (1990) Pharmacokintics
and dosage regemine of cephalexine in buffulo calves (Bubalis Bubalis following single
intravenous and intramusculer adminsteration Veterinary research commuincation 14
59-62
42 Goudah A (2008) Pharmacokinetic parameters of ceftriaxone after single intravenous
and intramuscular administration in camels (Camelus Dromedarius) Res Vet Sci Jun
84(3) 483-9
43 Sharma SK Srivastava AK and Deore DM (2006) Effect of Ecoli
lipopolysaccharides ndashinduced fever on disposition pattern of cefotaxime in buffalo calves
Veterinarski Arhiv 76(6) 537-545
44 Baggot JD (1977) Priniciple of pharmacokinetics In principle of drug disposition in
domestic animals The physiological Basis of veterinary Clinical Pharmacology 1st ed
WB Saunders Co Philadelphi PA 168-179
45 Karmaker UK Datta BK Patra PH Prashant M Suman S Sar TK Chakaborty
AK and mandal KT (2011) Disposition kinetics of ceftizoxime in healthy and mastitic
goats after intravenous adminsteration Pharmacologyonline 3 935-946
46 Ringger NC Pearson EG Gronwall R Kohlepp S J (1996) Pharmacokinetics of
ceftriaxone in healthy horses Equine Vet J Nov 28(6) 476-9
47 Prawez S Raina R Dimitrova D panka NK Ahanger AA Verma PK (2010) The
pharmacokinetics of cefipime in goats following single dose iv and im adminsteration
Turk j vet Anima Sci 34(5) 427-431
48 Baggot JD (1980) Distribution of antimicrobial agents in normal and diseased animals
JAVMA 19(76) 1085-1090
49 Haddad N S Pedersoli W M Ravis W R Fazeli M H and Carson Jr R L (1985)
Pharmacokinetics of gentamicin at steady-state in ponies serum urine and endometrial
concentrations Am J Vet Res 46(6) 1268-1271
50 Gupta JK Chaudhary RK and Dumka VK (2008) Pharmacokinetics after single
intramuscuker adminsrerarion and in-vitro binding plasma protein of cefoprazone in cross
bred calves Veterinaski Arhiv 78(5) 441-448
51 Al Taher AY (2010) Pharmacokinetics of cefquinome in camels J An Vet Ad 9(4)
848-852
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52 Rajput N Dumka V K and Sandhu HS (2012) Pharmacokinetics and in- vitro
plasma protein binding of cefpirome in cattle Veterinaski Arhiv 82(1) 1-9
53 RebueltoM Albarellos G Ambros L Kreil V Montoya L Bonafine R Otero P
Hallu R (2002) Pharmacokinetics of ceftriaxone administered by the intravenous
intramuscular or subcutaneous routes to dogs J Vet Pharmacol Ther Feb 25(1) 73-6
54 Patel RB Bhavsar SK Solanki PF Patel JH Varia RD Modi Falguni D and
Patel MD (2013) Pharmacokinetics of cefpirome following intravenous and
intramuscular administration in cow calves Sci Int 1(11) 371-374
55 Maradiya J J Goriya H V Bhavsar S K Patel U D and Thaker A M (2010)
Pharmacokinetics of ceftriaxone in calves Veterinarski arhiv 80(1) 1-9
56 Inges R MJ Fillastre J Godin M Leroy A and Humbert G (1982) The
Pharmacokinetics of cefotaxime and its metabolites in subjects with normal and impaired
renal function Clin Infect Dis (4) 379-391
57 Mcelroy D Ravis W R and Clark C H (1986) Pharmacokinetics of cefotaxime in
the domestic cats Am J Vet Res 47(1) 86-88
58 El-Sayed MG Atef M and El-Komy AA (1994) Disposition kinetic of cephradine in
normal and Escherichia coli infected goats Dtsch Tierarztl Wochenschr 101(2) 56-60
59 Soback S and Ziv G (1988) Pharmacokinetics and bioavailability of ceftriaxone
administered intravenously and intramuscularly to calves Am J Vet Res 49 535-538
60 Sharma S K and Srivastava A K (2003) Cefotaxime pharmacokinetics in male
buffalo calves following multiple dosing Veterinarski arhiv 73(4) 191-197
61 Abdulgafar O J Shaibu O B and Emmanuel U E (2011) Effect of Salmonella
typhymurium infection on the pharmacokinetics of ceftriaxone in sokoto red goats Niger
J Basic Applied Sci 19(1) 49-54
62 Ranjan R Birendra K R Amita R and Sanjeet K S (2011) Effect of Effect of E coli E
coli endotoxin induced fever on the pharmacokinetic profile and dosage regimen of
ceftriaxone in sheep (Ovis aries) Veterinarski arhiv 81(4) 423-432
63 Etuk EU and Onyeyili PA (2006) The effect of Salmonella infection on the plasma
kinetic of chloramphenicol in the sokoto red goats Inter J Pharmacol 2(1) 28-32
64 Wang E Bergeron Y and Bergeron MG (2005) Ceftriaxone pharmacokinetics in
interleukin-10-treated murine pneumococcal pneumonia J Antimicrob Chemother 55
721ndash726
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65 El-Sayed MG Hatem ME and El-Komy AA (1989) Disposition kinetic of
gentamicin in normal and endometric cow using microbiological assay Dtsch Tierarztl
Wochenschr 96(8) 412-415
66 Aramyona JJ Mora J Fraile LJ Garcia MA Abadia AR and Breganate MA
(1996) Penetration of enrofloxacin and ciprofloxacin into breast milk and
pharmacokinetics of the drugs in lacating rabbits and neonatal offspring Am J Vet Res
57(4) 547-553
67 Rusmussen F (1966) Studies on the mammary excretion and absorbtion of drugs Vet
Rec (87) 14-18
68 Alkinson A and Begg E (1990) Prediction of drug distribution into human milk from
physicochemical characteristics Clin Pharmacokinet 18(2) 151-167
69 Kenneth F (1997) Drug distribution in human milk Aust Prescr 20(2) 35-40
70 Aleksić M Savić V Popović G Burić N and Kapetanović V (2005) Acidity
constants of cefetamet cefotaxime and ceftriaxone the effect of the substituent at C3
position J Pharm Biomed Anal 39(3-4) 752-756
71 Prades M Brown M P Gronwall R and Miles N S (1988) Pharmacokinetics of
sodium cephapirin in lactating dairy cows Am J Vet Res 49(11) 1888-1890
72 Holazo A A Patel I H Weinfeld R E Konikoff J J and Parsonnet M (1986)
Ceftriaxone pharmacokinetics following multiple intramuscular dosing Euro J Clin
Pharmacol 30(1) 109-112
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (7) Urineserum concentrations ratios of ceftriaxone following repeated ntramuscular injection of 20 mg
ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats
(n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
229plusmn 163 1448plusmn0743 1885plusmn159 1125plusmn0484 533plusmn0260 1050plusmn358 175plusmn0380 4146plusmn116 ------- ------ Before
741plusmn0063 plusmn01553 58plusmn0242 plusmn0149390 422plusmn0206 683plusmn0106 245plusmn0092 667plusmn0306 0510plusmn0081 559plusmn0181 050
651plusmn0243 plusmn0065031 637plusmn0373 plusmn014431 565plusmn0243 plusmn0085300 360plusmn0303 plusmn0110312 279plusmn0121 534plusmn0248 1
836plusmn0150 plusmn00476322 862plusmn0180 plusmn010463 942plusmn0166 plusmn0130631 217plusmn0303 727plusmn0256 508plusmn0186 plusmn01680340 2
939plusmn0235 plusmn01580344 1006plusmn0710 plusmn00750310 999plusmn0542 plusmn02850344 565plusmn0223 641plusmn0241 48plusmn0164 plusmn014834 4
1005plusmn0418 2plusmn018813 1097plusmn0641 plusmn03979300 993plusmn0921 plusmn0252931 619plusmn0483 plusmn0362933 167plusmn0101 642plusmn0644 6
1091plusmn0649 plusmn075332339 1171plusmn0980 995plusmn0415 925plusmn0593 plusmn05593433 886plusmn0408 plusmn02510311 2055plusmn0311 plusmn02046310 8
2392plusmn129 plusmn032731396 1794plusmn0228 1222plusmn124 1418plusmn109 plusmn026733336 580plusmn0397 plusmn03951326 227plusmn0452 plusmn02740316 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
Table (8) Creatinine clearance (mlmin10kgbwt) following repeated intramuscular injection of 20 mg ceftriaxonekgbwt
twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats (n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1115plusmn0703 2265plusmn167 481plusmn0409 672plusmn0817 669plusmn0672 1202plusmn0777 695plusmn0634 1724plusmn179 ----------- ------ Before
0703plusmn0091 147plusmn0305 0718plusmn0141 251plusmn0707 0547plusmn0055 0699plusmn0092 0802plusmn0099 103plusmn0106 295plusmn0124 0458plusmn0037 050
101plusmn0075 161plusmn0093 131plusmn0099 264plusmn0217 161plusmn0146 373plusmn0499 247plusmn0110 4755plusmn0582 214plusmn0234 103plusmn0166 1
157plusmn0198 387plusmn0340 173plusmn0501 267plusmn0217 187plusmn0563 287plusmn0499 451plusmn0223 972plusmn105 263plusmn0399 169plusmn0454 2
wwwwjppscom Vol 5 Issue 02 2016
1445
Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
184plusmn0095 346plusmn0444 173plusmn0501 436plusmn0599 383plusmn0299 682plusmn0584 328plusmn0253 119plusmn153 123plusmn0057 292plusmn0742 4
221plusmn0242 411plusmn0661 241plusmn0186 663plusmn0584 308plusmn0234 422plusmn0314 353plusmn0393 548plusmn0901 105plusmn0057 264plusmn0294 6
261plusmn0295 476plusmn0339 319plusmn0273 753plusmn0676 106plusmn0207 0773plusmn0049 228plusmn0175 456plusmn0340 206plusmn0160 404plusmn0419 8
310plusmn0218 409plusmn0434 3264plusmn0153 669plusmn0476 209plusmn0189 235plusmn0337 217plusmn0143 377plusmn0342 240plusmn0218 6055plusmn0176 12
Between normal and diseased
Plt 005 Plt001 Plt0001
Table (9) Ceftriaxone clearance (mlmin10kgbwt following repeated intramuscular injection of 20 mg ceftriaxone kgbwt
twice in normal and experimentally Salmonella typhimurim infected goats (n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1048plusmn121 0557plusmn684 895plusmn113 0547plusmn560 238plusmn0222 103plusmn 480 0668plusmn0157 0173plusmn216 -------- ----------- Before
156plusmn0251 43204plusmn3322 0936plusmn0162 43211plusmn3334 0473plusmn0037 43469plusmn43964 0300plusmn0028 43341plusmn080 0190plusmn0137 43400plusmn43642 050
166plusmn0079 43323plusmn3311 157plusmn0178 43419plusmn3301 137plusmn0115 43311plusmn33022 0883plusmn0054 43341plusmn 133 0616plusmn0153 43120plusmn3301 1
254plusmn0272 43361plusmn3391 222plusmn0093 4331plusmn3390 243plusmn0180 43209plusmn3309 183plusmn0149 43310plusmn2340 128plusmn0153 43312plusmn3390 2
181plusmn0136 43339plusmn3316 161plusmn0129 433plusmn3329 144plusmn0100 43412plusmn3349 0821plusmn0072 0063plusmn0977 0654plusmn0065 43400plusmn4306 4
160plusmn0177 43393plusmn336 152plusmn0200 43416plusmn331 135plusmn0118 4332plusmn3322 0897plusmn0052 43304plusmn3330 0212plusmn0022 43460plusmn43112 6
153plusmn0049 43291plusmn234 163plusmn0242 43346plusmn3300 0891plusmn0272 43306plusmn3310 108plusmn0071 43416plusmn04310 0229plusmn0046 43490plusmn43916 8
340plusmn0522 43214plusmn2341 249plusmn0150 43112plusmn3393 186plusmn0159 43320plusmn336 0773plusmn0094 43390plusmn 134 0264plusmn0043 43400plusmn 54369 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
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1446
Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
Table (10) Ceftriaxone clearancecreatinine clearance following repeated ntramuscular injection of 20 mg
ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats
(n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
0934plusmn0083 0305plusmn0013 183plusmn0116 0864plusmn0098 0358plusmn0018 0279plusmn0047 0099plusmn0020 0127plusmn0001 ------- ----------- Before
220plusmn0115 0819plusmn0044 131plusmn00414 0458plusmn0029 0876plusmn0063 126plusmn0068 0361plusmn0011 0813plusmn0031 0018plusmn0003 108plusmn0062 050
164plusmn0078 0818plusmn0029 118plusmn0068 0546plusmn0027 0858plusmn0052 0407plusmn0041 0331plusmn0009 0287plusmn0025 0324plusmn0011 0909plusmn0187 1
161plusmn0044 0488plusmn0005 232plusmn128 0329plusmn0027 169plusmn0464 0686plusmn0050 0409plusmn0020 0220plusmn0029 0512plusmn0077 266plusmn177 2
0933plusmn0024 0394plusmn0005 0948plusmn0062 0296plusmn0007 0381plusmn0027 0160plusmn0008 0235plusmn0014 0083plusmn0006 0528plusmn0028 0362plusmn0041 4
0726plusmn0018 0411plusmn0028 0639plusmn0066 0204plusmn0006 0446plusmn0034 0286plusmn0008 0238plusmn0019 0214plusmn0006 020plusmn0013 0382plusmn0028 6
0609plusmn0072 0425plusmn0036 0508plusmn0052 0192plusmn0009 0524plusmn0146 174plusmn0083 0477plusmn0015 0213plusmn00018 0109plusmn0185 0222plusmn0006 8
108plusmn0128 0496plusmn0012 0942plusmn0004 0265plusmn0030 0891plusmn0056 0706plusmn0103 0351plusmn0022 0354plusmn0018 0111plusmn0021 0098plusmn0018 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
DISCUSSION
In the present investigation intravenous injection of 20 mg ceftriaxonekgbwt in normal goats the drug showed high serum level
(92plusmn 0408 μgml) at 5 minutes post-injection then its concentration was decreased gradually till reached its minimum level (18
plusmn0816μgml) at 8hours post-injection
wwwwjppscom Vol 5 Issue 01 2016
1447
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
In the present investigation the intravenous injection of 20 mg ceftriaxonekgbwt In normal
goats showed that the drug disposition best fitted a two-compartments- open model a
compartment of plasma and rapid equilibrating tissues and a deeper slower compartment
The obtained result is consistent with those reported for ceftriaxone in lactating goats[9]
lactating ewe[25]
domestic cat[15]
calves[26]
and patanwadi sheep[8]
Also this phenomenon is
in agreement with those reported for other cephalosporines as ceftazidime in a rabbit[27]
cefepime in dog and neonatal foals[28]
ewes[29]
ceftriaxone in goats[9]
cefipime in calves[30]
ceftiofur in cross-bred friesian cattle[31]
cefipime in calves[32]
ceftiofur in cows[33]
cefpirome
in cross-bred calves[3]
cefazidime in goats[35]
and cefquinome in sheep and goats[36]
cefipime
in chickens[37]
Ceftriaxone was distributed after intravenous injection with a distribution phase (α) equal to
656 per hour with a short distribution half ndash life [t05 (α)] equal to 0104 hour The shorter
distribution half-life of ceftriaxone in goats suggested the rapid distribution of the drug in
body tissue and fluid and that nearly similar to that recorded for ceftriaxone in lactating
goats(012 hour)[9]
for ceftriaxone in lactating ewes (0152 hour)[2]
and for ceftriaxone in
calves( 013hour)[26]
The rapid distribution of ceftriaxone in goats is supported by high rate constant of transfer of
the drug from central to peripheral compartment [K12 = 353 h-1
] as compared to the rate
constant of transfer of the drug from peripheral to central compartment [K21= 295 h-1
] This
value is nearly similar to those reported for cefotaxime in goats (K21=327 h-1
)[38]
On contrast
this value was higher than those recorded for ceftriaxone in lactating goats (K21=143 h-1
)[9]
in
lactating ewes (K21=125 h-1
)[25]
and in domestic cats (K21=154 h-1
)[15]
The apparent volume of distribution of ceftriaxone was (0355plusmn0004LKg) this value is
nearly similar to that recorded for cefaronide in sheep(039 LKg)[7]
cefotaxime in dog (048
lkg)[39]
in goat (051 lkg)
[40] for caphalexin in buffalo calves (041 Lkg)
[41] for cefipime in
ewes and calves (032 lkg) (043Lkg)[29]
and[30]
respectively For ceftriaxone in domestic
cats (057Lkg)[15]
in camel (032Lkg)[42]
On the other hand this result is differ than that
reported for cefotaxime in buffalo calves (117Lkg)[43]
High value of the volume of
distribution suggested extensive penetration power Drug with volume of distribution greater
than one literkilogram indicated wide distribution or extensive tissue binding or both[44]
The
apparent volume of distribution in the present study indicated moderate tissue penetrating
power This result agreed with[15]
for ceftriaxone in domestic cats
wwwwjppscom Vol 5 Issue 01 2016
1448
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
Ceftriaxone is eliminated in the current study following a single intravenous injection with
elimination half ndashlife [t 05(β)] equal to 519 hours This observation is nearly agreed with the
data recorded for ceftizoxime in goats (624hours)[45]
On contrast this value was longer than
that reported for ceftriaxone in lactating ewe (175hours)[25]
for cefaronide in sheep (17
hours)[7]
For cephalexin in buffulo calves (216hours)[41]
for ceftriaxone in healthy horse
(162hours)[46]
also this value is longer than that recorded for ceftriaxone in lactating goats
(144hours)[9]
for cefipime in goats (186hours)[47]
The rate of total body clearance of ceftriaxone following a single intravenous injection is
0048 lkgh which equal to data reported for ceftizoxime in lactating goats (005Lkgh)[45]
On contrast this value is lower than that reported for ceftriaxone in buffulo calves lactating
goats buffulo calves (Bubalus bubalis) goats (capra hircus) patanwadi sheep (026 Lkgh)
(395 Lkgh) (440 Lkgh) (450 Lkgh) (391 Lkgh)[12913118]
respectively
The variation in total body clearance might be attributed to specific interspecies variation
handling of the drug method used healthy status of the animal[48]
The difference between values calculated for pharmacokinetic parameters may be attributed
to animal species the drug formulation employed the age the size or sex o l lf the animal
or even inter individual variation and also due to method of analysis of the drug[49]
Following a single intramuscular injection of 20 mg ceftriaxonekg bwt In normal goats the
drug reached its peak serum concentrations after one hour of injection with value
of(41μgml) Ceftriaxone could be detected in serum in a therapeutic level (263μgml) at 12
hours post-injection The reported peak serum concentrations neerly similar to that reported
for cephalexin in buffulo calves (457 microgml)[41]
These results is differed than those reported
for ceftriaxone in cross breed calves (188 microgml at 30 min[16]
in Kangro breed of goats
(Capra Hircus) (2640 microgml at 20 min[10][50]
found after intramuscular administration of
ceforazone peak plasma concentration was (976 microgml) at 45min This result was also higher
than that recorded for ceftriaxone in buffalo calves (158 microgml)[13]
The calculated maximum serum concentration (Cmax) is (40015 microgml) at maximum time
(tmax) of 157 hours The reported (Cmax) agreed with the data reported for cefipime in goats
(4932 microgml[47]
The reported maximum serum concentration (Cmax) is higher than that
reported for ceftriaxone in lactating goats(236 microgml)[9]
in lactating ewes (1722 microgml[25]
in
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
goats (2151 microgml)[11]
for cefquinome in camels (123 microgml)[51]
for ceftriaxone in calves
(1534 microgml)[26]
in patanwadi sheep (1553 microgml)[8]
for cefpirome in cattle (101 microgml)[52]
And for ceftiofur in chickens (2594 μgml)[37]
On the other hand the result was lower than
that reported by[6]
who observed the maximum serum concentration (Cmax) of ceftriaxone in
human after ntramuscular administration was (805 microgml) also it was lower than that
reported for ceftriaxone in dog (11510 microgml)[53]
in domestic cats (5440 microgml)[15]
and for
ceftazoxime in goats (8878 microgml)[45]
The reported [tmax] is neerly similar to that reported for ceftriaxone (104hours)in lactating
ewes by[25]
On contrast it is longer than those reported for ceftriaxone in dogs
(129hours)[53]
for ceftriaxone in lactating goats (07hours)[9]
also the result was longer than
that reported for ceftriaxone in domestic cats (033hours)[15]
in buffulo calves (05 hours)[13]
and for cefpirome in cattle (075hours)[52]
The reported [tmax] is shorter than those reported
for cefquinome in camels (425hours)[51]
in sheep and goats (261 and 262 hours)[36]
and for
ceftiofur in chickens (251 hours)[37]
The elimination half life [t05(β)]
following a single intramuscular administration was 1804 hours This value is nearly agreed
with that recorded for cefquinomein camels (1024hours)[52]
On contrast this result is longer
than that reported for cephalexin in buffalo calves (243hours)[41]
for ceftriaxone in lactating
ewes (177hours)[25]
in buffalo calves (438hours)[13]
in goats (203 hours)[11]
and for
cefipime in goats (165 hours)[47]
The rate of total body clearance of ceftriaxone following a single intramuscular injection is
0043lkgh This value was lower than that reported for ceftriaxone in buffulo calves
(401Lkgh)[13]
in goats (304 Lkgh)[11]
and in sheep (222 Lkgh)[8]
Bioavailability is the fraction of the drug administered by non vascular rout that gains
accesses to the systemic circulation The obtained result revealed that the calculated systemic
bioavailability percent was 6128 It is equal to that recorded for cefpirome in cow calves
(61)[54]
It is nearly equal to that recorded for ceftriaxone in sheep (64)[8]
On the other
hand this value is higher than those recorded for cefperazone in crossbred calves (481)[50]
for ceftriaxone in goats (59)[11]
in calves (47)[55]
On contrast this value is lower than
those reported for cefotaxime in two cats 982 and 93)[57]
for cephradine in goats
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
(739)[58]
for ceftazidime in a rabbit (966)[27]
for ceftriaxone in lactating goats (85)[9]
in lactating ewes (836)[25]
in domestic cats 8572[15]
for cefipime in goats 8645[47]
for ceftriaxone in buffulo calves 702[13]
and for ceftiofur in chickens 8890[37]
Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium
infected goats twics dialy for five days revealed that the drug could be detected in a
therapeutic level for 12hours following repeated intramuscular administrations and exceeded
the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]
The relative higher serum concentrations of ceftriaxone after the last dose compared to the
first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12
hours intervals for five consecutive days These observations agreed with data reported by[36]
on comparing the data of serum levels of repeated intramuscular injections with first
intramuscular injection it was revealed that repeated intramuscular injections of cefquinome
have cumulative effect in both species sheep and goats
The obtained result is inconsistent with that reported by[56]
who found thatwhen cefotaxime
was administered repetitively in patients the ratio of maximal serum levels after the last dose
to those after the first dose demonstrated minimal accumulation of intact drug and by[60]
who
found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in
buffalo calves
The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium
infected goats are significantly lower than those in normal goats following repeated
intramuscular injection These lower blood concentrations in Salmonella typhimurium
infected goats might be attributed to the higher penetrating power of ceftriaxone to the
diseased tissues[48]
This phenomenon is similar to data recorded by[61]
who suggested that
Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of
ceftriaxone These alterations might be due to fever and inflammation induced by
infections[59]
proved that the serum concentrations of cephradine following intramuscular
administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after
each intramuscular dose with a lower significant values recorded in Escherichia-coli infected
goats than in normal goatsAlso similer to that reported by[62]
who observed that the
maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep
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1451
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
in comparison to normal sheepOn contrast[43]
reported that peak plasma level of cefotaxime
in febrile buffalo calves was higher than healthy buffalo calves
In this study the total body clearance (CLtot) in normal goats are significantly lower than in
Salmonella typhimurium infected goats This result supported by[61]
and[63]
fever and
inflammation are cardinal features in bacterial infection which may in turn caused an
increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all
these could lead to increased in the rate at which the drug was delivered to both organs which
were important sites of drug excretion This might somewhat explain the increase in the total
body clearance in infected goats This result is differ than that reported by[64]
who observed
that the clearance of ceftriaxone was significantly reduced in infected mice than in non
infected animals
The highest concentrations of ceftriaxone in milk are recorded 4 hours after each
intramuscular injection with a significant lower value in Salmonella typhimurium infected
goats than in normal goats This might be attributed to accumulation of drug in the inflammed
tissues[48]
This result is similar to those reported by[6559]
who found that milk concentrations
of gentamicin and cephradine were significantly lower in infected goats and cattle than in
normal ones respectively
The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the
non-ionic passive diffusion principle[66]
reported that most drug cross-lipid membranes by
passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly
influenced by the physicochemical properties of the drug[6768]
Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum
ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the
physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]
Milk
contains substantially more lipid and less protein than serum and is slightly more acidic
Therefore drugs which tend to concentrated in milk are weak bases with low serum protein
binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide
and aminothiazole also possesses an hydroxytriazinone group as new and additional
ionization center[70]
these compounds are sufficiently lipid- soluble to be able to penetrate
tissues
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
The dose of ceftriaxone used in the present study induced therapeutically concentrations in
milk These concentrations suggested that ceftriaxone would be efficacious in treatment of
mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily
for 3-5 days
The study showed that the urine concentrations of ceftriaxone are greater than the concurrent
serum concentrations following intramuscular injection This observation is similar to those
reported in cows after cephapirin administrations[71]
In the present study urine concentrations of ceftriaxone increased with the repetition of
dosing This observation supported by[72]
after repeated intramuscular administrations of
ceftriaxone in healthy volunteeres
The mean peak urine concentrations of ceftriaxone were reached 2 hours after each
intramuscular injection The lower urine ceftriaxone concentrations in Salmonella
typhimurium infected goats than in normal goats might be attributed to the accumulation of
the drug in the inflamed tissues[48]
The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower
ratio in Salmonella typhimurium infected goats than in normal goats at different time of
sampling This indicates that glomerular filteration seemed to be the main pathway of
ceftriaxone elimination This observation supported by[59]
who found that the ratio between
cephradine clearance from blood of goats to creatinine clearance showed a marked decrease
in Escherichia-coli infected goats than in normal goats This indicated that glomerular
filteration seemed to be the main pathway of cephradine elimination with a limited rate of
tubular reabsorption
CONCLUSION
The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value
referred a better absorption of ceftriaxone from its site of intramuscular administration The
high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular
administrations suggested that ceftriaxone could be used for treatment of mastitis caused by
Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats
The high concentrations of ceftriaxone in urine after repeated intramuscular administrations
suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections
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1453
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in
goats
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
184plusmn0095 346plusmn0444 173plusmn0501 436plusmn0599 383plusmn0299 682plusmn0584 328plusmn0253 119plusmn153 123plusmn0057 292plusmn0742 4
221plusmn0242 411plusmn0661 241plusmn0186 663plusmn0584 308plusmn0234 422plusmn0314 353plusmn0393 548plusmn0901 105plusmn0057 264plusmn0294 6
261plusmn0295 476plusmn0339 319plusmn0273 753plusmn0676 106plusmn0207 0773plusmn0049 228plusmn0175 456plusmn0340 206plusmn0160 404plusmn0419 8
310plusmn0218 409plusmn0434 3264plusmn0153 669plusmn0476 209plusmn0189 235plusmn0337 217plusmn0143 377plusmn0342 240plusmn0218 6055plusmn0176 12
Between normal and diseased
Plt 005 Plt001 Plt0001
Table (9) Ceftriaxone clearance (mlmin10kgbwt following repeated intramuscular injection of 20 mg ceftriaxone kgbwt
twice in normal and experimentally Salmonella typhimurim infected goats (n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
1048plusmn121 0557plusmn684 895plusmn113 0547plusmn560 238plusmn0222 103plusmn 480 0668plusmn0157 0173plusmn216 -------- ----------- Before
156plusmn0251 43204plusmn3322 0936plusmn0162 43211plusmn3334 0473plusmn0037 43469plusmn43964 0300plusmn0028 43341plusmn080 0190plusmn0137 43400plusmn43642 050
166plusmn0079 43323plusmn3311 157plusmn0178 43419plusmn3301 137plusmn0115 43311plusmn33022 0883plusmn0054 43341plusmn 133 0616plusmn0153 43120plusmn3301 1
254plusmn0272 43361plusmn3391 222plusmn0093 4331plusmn3390 243plusmn0180 43209plusmn3309 183plusmn0149 43310plusmn2340 128plusmn0153 43312plusmn3390 2
181plusmn0136 43339plusmn3316 161plusmn0129 433plusmn3329 144plusmn0100 43412plusmn3349 0821plusmn0072 0063plusmn0977 0654plusmn0065 43400plusmn4306 4
160plusmn0177 43393plusmn336 152plusmn0200 43416plusmn331 135plusmn0118 4332plusmn3322 0897plusmn0052 43304plusmn3330 0212plusmn0022 43460plusmn43112 6
153plusmn0049 43291plusmn234 163plusmn0242 43346plusmn3300 0891plusmn0272 43306plusmn3310 108plusmn0071 43416plusmn04310 0229plusmn0046 43490plusmn43916 8
340plusmn0522 43214plusmn2341 249plusmn0150 43112plusmn3393 186plusmn0159 43320plusmn336 0773plusmn0094 43390plusmn 134 0264plusmn0043 43400plusmn 54369 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
Table (10) Ceftriaxone clearancecreatinine clearance following repeated ntramuscular injection of 20 mg
ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats
(n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
0934plusmn0083 0305plusmn0013 183plusmn0116 0864plusmn0098 0358plusmn0018 0279plusmn0047 0099plusmn0020 0127plusmn0001 ------- ----------- Before
220plusmn0115 0819plusmn0044 131plusmn00414 0458plusmn0029 0876plusmn0063 126plusmn0068 0361plusmn0011 0813plusmn0031 0018plusmn0003 108plusmn0062 050
164plusmn0078 0818plusmn0029 118plusmn0068 0546plusmn0027 0858plusmn0052 0407plusmn0041 0331plusmn0009 0287plusmn0025 0324plusmn0011 0909plusmn0187 1
161plusmn0044 0488plusmn0005 232plusmn128 0329plusmn0027 169plusmn0464 0686plusmn0050 0409plusmn0020 0220plusmn0029 0512plusmn0077 266plusmn177 2
0933plusmn0024 0394plusmn0005 0948plusmn0062 0296plusmn0007 0381plusmn0027 0160plusmn0008 0235plusmn0014 0083plusmn0006 0528plusmn0028 0362plusmn0041 4
0726plusmn0018 0411plusmn0028 0639plusmn0066 0204plusmn0006 0446plusmn0034 0286plusmn0008 0238plusmn0019 0214plusmn0006 020plusmn0013 0382plusmn0028 6
0609plusmn0072 0425plusmn0036 0508plusmn0052 0192plusmn0009 0524plusmn0146 174plusmn0083 0477plusmn0015 0213plusmn00018 0109plusmn0185 0222plusmn0006 8
108plusmn0128 0496plusmn0012 0942plusmn0004 0265plusmn0030 0891plusmn0056 0706plusmn0103 0351plusmn0022 0354plusmn0018 0111plusmn0021 0098plusmn0018 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
DISCUSSION
In the present investigation intravenous injection of 20 mg ceftriaxonekgbwt in normal goats the drug showed high serum level
(92plusmn 0408 μgml) at 5 minutes post-injection then its concentration was decreased gradually till reached its minimum level (18
plusmn0816μgml) at 8hours post-injection
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
In the present investigation the intravenous injection of 20 mg ceftriaxonekgbwt In normal
goats showed that the drug disposition best fitted a two-compartments- open model a
compartment of plasma and rapid equilibrating tissues and a deeper slower compartment
The obtained result is consistent with those reported for ceftriaxone in lactating goats[9]
lactating ewe[25]
domestic cat[15]
calves[26]
and patanwadi sheep[8]
Also this phenomenon is
in agreement with those reported for other cephalosporines as ceftazidime in a rabbit[27]
cefepime in dog and neonatal foals[28]
ewes[29]
ceftriaxone in goats[9]
cefipime in calves[30]
ceftiofur in cross-bred friesian cattle[31]
cefipime in calves[32]
ceftiofur in cows[33]
cefpirome
in cross-bred calves[3]
cefazidime in goats[35]
and cefquinome in sheep and goats[36]
cefipime
in chickens[37]
Ceftriaxone was distributed after intravenous injection with a distribution phase (α) equal to
656 per hour with a short distribution half ndash life [t05 (α)] equal to 0104 hour The shorter
distribution half-life of ceftriaxone in goats suggested the rapid distribution of the drug in
body tissue and fluid and that nearly similar to that recorded for ceftriaxone in lactating
goats(012 hour)[9]
for ceftriaxone in lactating ewes (0152 hour)[2]
and for ceftriaxone in
calves( 013hour)[26]
The rapid distribution of ceftriaxone in goats is supported by high rate constant of transfer of
the drug from central to peripheral compartment [K12 = 353 h-1
] as compared to the rate
constant of transfer of the drug from peripheral to central compartment [K21= 295 h-1
] This
value is nearly similar to those reported for cefotaxime in goats (K21=327 h-1
)[38]
On contrast
this value was higher than those recorded for ceftriaxone in lactating goats (K21=143 h-1
)[9]
in
lactating ewes (K21=125 h-1
)[25]
and in domestic cats (K21=154 h-1
)[15]
The apparent volume of distribution of ceftriaxone was (0355plusmn0004LKg) this value is
nearly similar to that recorded for cefaronide in sheep(039 LKg)[7]
cefotaxime in dog (048
lkg)[39]
in goat (051 lkg)
[40] for caphalexin in buffalo calves (041 Lkg)
[41] for cefipime in
ewes and calves (032 lkg) (043Lkg)[29]
and[30]
respectively For ceftriaxone in domestic
cats (057Lkg)[15]
in camel (032Lkg)[42]
On the other hand this result is differ than that
reported for cefotaxime in buffalo calves (117Lkg)[43]
High value of the volume of
distribution suggested extensive penetration power Drug with volume of distribution greater
than one literkilogram indicated wide distribution or extensive tissue binding or both[44]
The
apparent volume of distribution in the present study indicated moderate tissue penetrating
power This result agreed with[15]
for ceftriaxone in domestic cats
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
Ceftriaxone is eliminated in the current study following a single intravenous injection with
elimination half ndashlife [t 05(β)] equal to 519 hours This observation is nearly agreed with the
data recorded for ceftizoxime in goats (624hours)[45]
On contrast this value was longer than
that reported for ceftriaxone in lactating ewe (175hours)[25]
for cefaronide in sheep (17
hours)[7]
For cephalexin in buffulo calves (216hours)[41]
for ceftriaxone in healthy horse
(162hours)[46]
also this value is longer than that recorded for ceftriaxone in lactating goats
(144hours)[9]
for cefipime in goats (186hours)[47]
The rate of total body clearance of ceftriaxone following a single intravenous injection is
0048 lkgh which equal to data reported for ceftizoxime in lactating goats (005Lkgh)[45]
On contrast this value is lower than that reported for ceftriaxone in buffulo calves lactating
goats buffulo calves (Bubalus bubalis) goats (capra hircus) patanwadi sheep (026 Lkgh)
(395 Lkgh) (440 Lkgh) (450 Lkgh) (391 Lkgh)[12913118]
respectively
The variation in total body clearance might be attributed to specific interspecies variation
handling of the drug method used healthy status of the animal[48]
The difference between values calculated for pharmacokinetic parameters may be attributed
to animal species the drug formulation employed the age the size or sex o l lf the animal
or even inter individual variation and also due to method of analysis of the drug[49]
Following a single intramuscular injection of 20 mg ceftriaxonekg bwt In normal goats the
drug reached its peak serum concentrations after one hour of injection with value
of(41μgml) Ceftriaxone could be detected in serum in a therapeutic level (263μgml) at 12
hours post-injection The reported peak serum concentrations neerly similar to that reported
for cephalexin in buffulo calves (457 microgml)[41]
These results is differed than those reported
for ceftriaxone in cross breed calves (188 microgml at 30 min[16]
in Kangro breed of goats
(Capra Hircus) (2640 microgml at 20 min[10][50]
found after intramuscular administration of
ceforazone peak plasma concentration was (976 microgml) at 45min This result was also higher
than that recorded for ceftriaxone in buffalo calves (158 microgml)[13]
The calculated maximum serum concentration (Cmax) is (40015 microgml) at maximum time
(tmax) of 157 hours The reported (Cmax) agreed with the data reported for cefipime in goats
(4932 microgml[47]
The reported maximum serum concentration (Cmax) is higher than that
reported for ceftriaxone in lactating goats(236 microgml)[9]
in lactating ewes (1722 microgml[25]
in
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
goats (2151 microgml)[11]
for cefquinome in camels (123 microgml)[51]
for ceftriaxone in calves
(1534 microgml)[26]
in patanwadi sheep (1553 microgml)[8]
for cefpirome in cattle (101 microgml)[52]
And for ceftiofur in chickens (2594 μgml)[37]
On the other hand the result was lower than
that reported by[6]
who observed the maximum serum concentration (Cmax) of ceftriaxone in
human after ntramuscular administration was (805 microgml) also it was lower than that
reported for ceftriaxone in dog (11510 microgml)[53]
in domestic cats (5440 microgml)[15]
and for
ceftazoxime in goats (8878 microgml)[45]
The reported [tmax] is neerly similar to that reported for ceftriaxone (104hours)in lactating
ewes by[25]
On contrast it is longer than those reported for ceftriaxone in dogs
(129hours)[53]
for ceftriaxone in lactating goats (07hours)[9]
also the result was longer than
that reported for ceftriaxone in domestic cats (033hours)[15]
in buffulo calves (05 hours)[13]
and for cefpirome in cattle (075hours)[52]
The reported [tmax] is shorter than those reported
for cefquinome in camels (425hours)[51]
in sheep and goats (261 and 262 hours)[36]
and for
ceftiofur in chickens (251 hours)[37]
The elimination half life [t05(β)]
following a single intramuscular administration was 1804 hours This value is nearly agreed
with that recorded for cefquinomein camels (1024hours)[52]
On contrast this result is longer
than that reported for cephalexin in buffalo calves (243hours)[41]
for ceftriaxone in lactating
ewes (177hours)[25]
in buffalo calves (438hours)[13]
in goats (203 hours)[11]
and for
cefipime in goats (165 hours)[47]
The rate of total body clearance of ceftriaxone following a single intramuscular injection is
0043lkgh This value was lower than that reported for ceftriaxone in buffulo calves
(401Lkgh)[13]
in goats (304 Lkgh)[11]
and in sheep (222 Lkgh)[8]
Bioavailability is the fraction of the drug administered by non vascular rout that gains
accesses to the systemic circulation The obtained result revealed that the calculated systemic
bioavailability percent was 6128 It is equal to that recorded for cefpirome in cow calves
(61)[54]
It is nearly equal to that recorded for ceftriaxone in sheep (64)[8]
On the other
hand this value is higher than those recorded for cefperazone in crossbred calves (481)[50]
for ceftriaxone in goats (59)[11]
in calves (47)[55]
On contrast this value is lower than
those reported for cefotaxime in two cats 982 and 93)[57]
for cephradine in goats
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
(739)[58]
for ceftazidime in a rabbit (966)[27]
for ceftriaxone in lactating goats (85)[9]
in lactating ewes (836)[25]
in domestic cats 8572[15]
for cefipime in goats 8645[47]
for ceftriaxone in buffulo calves 702[13]
and for ceftiofur in chickens 8890[37]
Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium
infected goats twics dialy for five days revealed that the drug could be detected in a
therapeutic level for 12hours following repeated intramuscular administrations and exceeded
the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]
The relative higher serum concentrations of ceftriaxone after the last dose compared to the
first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12
hours intervals for five consecutive days These observations agreed with data reported by[36]
on comparing the data of serum levels of repeated intramuscular injections with first
intramuscular injection it was revealed that repeated intramuscular injections of cefquinome
have cumulative effect in both species sheep and goats
The obtained result is inconsistent with that reported by[56]
who found thatwhen cefotaxime
was administered repetitively in patients the ratio of maximal serum levels after the last dose
to those after the first dose demonstrated minimal accumulation of intact drug and by[60]
who
found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in
buffalo calves
The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium
infected goats are significantly lower than those in normal goats following repeated
intramuscular injection These lower blood concentrations in Salmonella typhimurium
infected goats might be attributed to the higher penetrating power of ceftriaxone to the
diseased tissues[48]
This phenomenon is similar to data recorded by[61]
who suggested that
Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of
ceftriaxone These alterations might be due to fever and inflammation induced by
infections[59]
proved that the serum concentrations of cephradine following intramuscular
administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after
each intramuscular dose with a lower significant values recorded in Escherichia-coli infected
goats than in normal goatsAlso similer to that reported by[62]
who observed that the
maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
in comparison to normal sheepOn contrast[43]
reported that peak plasma level of cefotaxime
in febrile buffalo calves was higher than healthy buffalo calves
In this study the total body clearance (CLtot) in normal goats are significantly lower than in
Salmonella typhimurium infected goats This result supported by[61]
and[63]
fever and
inflammation are cardinal features in bacterial infection which may in turn caused an
increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all
these could lead to increased in the rate at which the drug was delivered to both organs which
were important sites of drug excretion This might somewhat explain the increase in the total
body clearance in infected goats This result is differ than that reported by[64]
who observed
that the clearance of ceftriaxone was significantly reduced in infected mice than in non
infected animals
The highest concentrations of ceftriaxone in milk are recorded 4 hours after each
intramuscular injection with a significant lower value in Salmonella typhimurium infected
goats than in normal goats This might be attributed to accumulation of drug in the inflammed
tissues[48]
This result is similar to those reported by[6559]
who found that milk concentrations
of gentamicin and cephradine were significantly lower in infected goats and cattle than in
normal ones respectively
The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the
non-ionic passive diffusion principle[66]
reported that most drug cross-lipid membranes by
passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly
influenced by the physicochemical properties of the drug[6768]
Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum
ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the
physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]
Milk
contains substantially more lipid and less protein than serum and is slightly more acidic
Therefore drugs which tend to concentrated in milk are weak bases with low serum protein
binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide
and aminothiazole also possesses an hydroxytriazinone group as new and additional
ionization center[70]
these compounds are sufficiently lipid- soluble to be able to penetrate
tissues
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
The dose of ceftriaxone used in the present study induced therapeutically concentrations in
milk These concentrations suggested that ceftriaxone would be efficacious in treatment of
mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily
for 3-5 days
The study showed that the urine concentrations of ceftriaxone are greater than the concurrent
serum concentrations following intramuscular injection This observation is similar to those
reported in cows after cephapirin administrations[71]
In the present study urine concentrations of ceftriaxone increased with the repetition of
dosing This observation supported by[72]
after repeated intramuscular administrations of
ceftriaxone in healthy volunteeres
The mean peak urine concentrations of ceftriaxone were reached 2 hours after each
intramuscular injection The lower urine ceftriaxone concentrations in Salmonella
typhimurium infected goats than in normal goats might be attributed to the accumulation of
the drug in the inflamed tissues[48]
The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower
ratio in Salmonella typhimurium infected goats than in normal goats at different time of
sampling This indicates that glomerular filteration seemed to be the main pathway of
ceftriaxone elimination This observation supported by[59]
who found that the ratio between
cephradine clearance from blood of goats to creatinine clearance showed a marked decrease
in Escherichia-coli infected goats than in normal goats This indicated that glomerular
filteration seemed to be the main pathway of cephradine elimination with a limited rate of
tubular reabsorption
CONCLUSION
The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value
referred a better absorption of ceftriaxone from its site of intramuscular administration The
high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular
administrations suggested that ceftriaxone could be used for treatment of mastitis caused by
Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats
The high concentrations of ceftriaxone in urine after repeated intramuscular administrations
suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in
goats
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administered intravenously and intramuscularly to calves Am J Vet Res 49 535-538
60 Sharma S K and Srivastava A K (2003) Cefotaxime pharmacokinetics in male
buffalo calves following multiple dosing Veterinarski arhiv 73(4) 191-197
61 Abdulgafar O J Shaibu O B and Emmanuel U E (2011) Effect of Salmonella
typhymurium infection on the pharmacokinetics of ceftriaxone in sokoto red goats Niger
J Basic Applied Sci 19(1) 49-54
62 Ranjan R Birendra K R Amita R and Sanjeet K S (2011) Effect of Effect of E coli E
coli endotoxin induced fever on the pharmacokinetic profile and dosage regimen of
ceftriaxone in sheep (Ovis aries) Veterinarski arhiv 81(4) 423-432
63 Etuk EU and Onyeyili PA (2006) The effect of Salmonella infection on the plasma
kinetic of chloramphenicol in the sokoto red goats Inter J Pharmacol 2(1) 28-32
64 Wang E Bergeron Y and Bergeron MG (2005) Ceftriaxone pharmacokinetics in
interleukin-10-treated murine pneumococcal pneumonia J Antimicrob Chemother 55
721ndash726
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65 El-Sayed MG Hatem ME and El-Komy AA (1989) Disposition kinetic of
gentamicin in normal and endometric cow using microbiological assay Dtsch Tierarztl
Wochenschr 96(8) 412-415
66 Aramyona JJ Mora J Fraile LJ Garcia MA Abadia AR and Breganate MA
(1996) Penetration of enrofloxacin and ciprofloxacin into breast milk and
pharmacokinetics of the drugs in lacating rabbits and neonatal offspring Am J Vet Res
57(4) 547-553
67 Rusmussen F (1966) Studies on the mammary excretion and absorbtion of drugs Vet
Rec (87) 14-18
68 Alkinson A and Begg E (1990) Prediction of drug distribution into human milk from
physicochemical characteristics Clin Pharmacokinet 18(2) 151-167
69 Kenneth F (1997) Drug distribution in human milk Aust Prescr 20(2) 35-40
70 Aleksić M Savić V Popović G Burić N and Kapetanović V (2005) Acidity
constants of cefetamet cefotaxime and ceftriaxone the effect of the substituent at C3
position J Pharm Biomed Anal 39(3-4) 752-756
71 Prades M Brown M P Gronwall R and Miles N S (1988) Pharmacokinetics of
sodium cephapirin in lactating dairy cows Am J Vet Res 49(11) 1888-1890
72 Holazo A A Patel I H Weinfeld R E Konikoff J J and Parsonnet M (1986)
Ceftriaxone pharmacokinetics following multiple intramuscular dosing Euro J Clin
Pharmacol 30(1) 109-112
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Sayed et al World Journal of Pharmacy and Pharmaceutical Sciences
Table (10) Ceftriaxone clearancecreatinine clearance following repeated ntramuscular injection of 20 mg
ceftriaxonekgbwt twice dialy for five consecutive days in normal and experimentally Salmonella typhimurim infected goats
(n=4)
Dose Time of
a administration
(h)
Ninth_
(XplusmnS E)
Seventh_
(XplusmnS E)
Fifth_
(XplusmnS E)
Third_
(XplusmnS E)
First_
(XplusmnS E)fi
S N S N S N N S N S S N
0934plusmn0083 0305plusmn0013 183plusmn0116 0864plusmn0098 0358plusmn0018 0279plusmn0047 0099plusmn0020 0127plusmn0001 ------- ----------- Before
220plusmn0115 0819plusmn0044 131plusmn00414 0458plusmn0029 0876plusmn0063 126plusmn0068 0361plusmn0011 0813plusmn0031 0018plusmn0003 108plusmn0062 050
164plusmn0078 0818plusmn0029 118plusmn0068 0546plusmn0027 0858plusmn0052 0407plusmn0041 0331plusmn0009 0287plusmn0025 0324plusmn0011 0909plusmn0187 1
161plusmn0044 0488plusmn0005 232plusmn128 0329plusmn0027 169plusmn0464 0686plusmn0050 0409plusmn0020 0220plusmn0029 0512plusmn0077 266plusmn177 2
0933plusmn0024 0394plusmn0005 0948plusmn0062 0296plusmn0007 0381plusmn0027 0160plusmn0008 0235plusmn0014 0083plusmn0006 0528plusmn0028 0362plusmn0041 4
0726plusmn0018 0411plusmn0028 0639plusmn0066 0204plusmn0006 0446plusmn0034 0286plusmn0008 0238plusmn0019 0214plusmn0006 020plusmn0013 0382plusmn0028 6
0609plusmn0072 0425plusmn0036 0508plusmn0052 0192plusmn0009 0524plusmn0146 174plusmn0083 0477plusmn0015 0213plusmn00018 0109plusmn0185 0222plusmn0006 8
108plusmn0128 0496plusmn0012 0942plusmn0004 0265plusmn0030 0891plusmn0056 0706plusmn0103 0351plusmn0022 0354plusmn0018 0111plusmn0021 0098plusmn0018 12
Between normal and diseased
Plt 005 Plt001 Plt0001
N= Normal S= Salmonella infected
DISCUSSION
In the present investigation intravenous injection of 20 mg ceftriaxonekgbwt in normal goats the drug showed high serum level
(92plusmn 0408 μgml) at 5 minutes post-injection then its concentration was decreased gradually till reached its minimum level (18
plusmn0816μgml) at 8hours post-injection
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
In the present investigation the intravenous injection of 20 mg ceftriaxonekgbwt In normal
goats showed that the drug disposition best fitted a two-compartments- open model a
compartment of plasma and rapid equilibrating tissues and a deeper slower compartment
The obtained result is consistent with those reported for ceftriaxone in lactating goats[9]
lactating ewe[25]
domestic cat[15]
calves[26]
and patanwadi sheep[8]
Also this phenomenon is
in agreement with those reported for other cephalosporines as ceftazidime in a rabbit[27]
cefepime in dog and neonatal foals[28]
ewes[29]
ceftriaxone in goats[9]
cefipime in calves[30]
ceftiofur in cross-bred friesian cattle[31]
cefipime in calves[32]
ceftiofur in cows[33]
cefpirome
in cross-bred calves[3]
cefazidime in goats[35]
and cefquinome in sheep and goats[36]
cefipime
in chickens[37]
Ceftriaxone was distributed after intravenous injection with a distribution phase (α) equal to
656 per hour with a short distribution half ndash life [t05 (α)] equal to 0104 hour The shorter
distribution half-life of ceftriaxone in goats suggested the rapid distribution of the drug in
body tissue and fluid and that nearly similar to that recorded for ceftriaxone in lactating
goats(012 hour)[9]
for ceftriaxone in lactating ewes (0152 hour)[2]
and for ceftriaxone in
calves( 013hour)[26]
The rapid distribution of ceftriaxone in goats is supported by high rate constant of transfer of
the drug from central to peripheral compartment [K12 = 353 h-1
] as compared to the rate
constant of transfer of the drug from peripheral to central compartment [K21= 295 h-1
] This
value is nearly similar to those reported for cefotaxime in goats (K21=327 h-1
)[38]
On contrast
this value was higher than those recorded for ceftriaxone in lactating goats (K21=143 h-1
)[9]
in
lactating ewes (K21=125 h-1
)[25]
and in domestic cats (K21=154 h-1
)[15]
The apparent volume of distribution of ceftriaxone was (0355plusmn0004LKg) this value is
nearly similar to that recorded for cefaronide in sheep(039 LKg)[7]
cefotaxime in dog (048
lkg)[39]
in goat (051 lkg)
[40] for caphalexin in buffalo calves (041 Lkg)
[41] for cefipime in
ewes and calves (032 lkg) (043Lkg)[29]
and[30]
respectively For ceftriaxone in domestic
cats (057Lkg)[15]
in camel (032Lkg)[42]
On the other hand this result is differ than that
reported for cefotaxime in buffalo calves (117Lkg)[43]
High value of the volume of
distribution suggested extensive penetration power Drug with volume of distribution greater
than one literkilogram indicated wide distribution or extensive tissue binding or both[44]
The
apparent volume of distribution in the present study indicated moderate tissue penetrating
power This result agreed with[15]
for ceftriaxone in domestic cats
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
Ceftriaxone is eliminated in the current study following a single intravenous injection with
elimination half ndashlife [t 05(β)] equal to 519 hours This observation is nearly agreed with the
data recorded for ceftizoxime in goats (624hours)[45]
On contrast this value was longer than
that reported for ceftriaxone in lactating ewe (175hours)[25]
for cefaronide in sheep (17
hours)[7]
For cephalexin in buffulo calves (216hours)[41]
for ceftriaxone in healthy horse
(162hours)[46]
also this value is longer than that recorded for ceftriaxone in lactating goats
(144hours)[9]
for cefipime in goats (186hours)[47]
The rate of total body clearance of ceftriaxone following a single intravenous injection is
0048 lkgh which equal to data reported for ceftizoxime in lactating goats (005Lkgh)[45]
On contrast this value is lower than that reported for ceftriaxone in buffulo calves lactating
goats buffulo calves (Bubalus bubalis) goats (capra hircus) patanwadi sheep (026 Lkgh)
(395 Lkgh) (440 Lkgh) (450 Lkgh) (391 Lkgh)[12913118]
respectively
The variation in total body clearance might be attributed to specific interspecies variation
handling of the drug method used healthy status of the animal[48]
The difference between values calculated for pharmacokinetic parameters may be attributed
to animal species the drug formulation employed the age the size or sex o l lf the animal
or even inter individual variation and also due to method of analysis of the drug[49]
Following a single intramuscular injection of 20 mg ceftriaxonekg bwt In normal goats the
drug reached its peak serum concentrations after one hour of injection with value
of(41μgml) Ceftriaxone could be detected in serum in a therapeutic level (263μgml) at 12
hours post-injection The reported peak serum concentrations neerly similar to that reported
for cephalexin in buffulo calves (457 microgml)[41]
These results is differed than those reported
for ceftriaxone in cross breed calves (188 microgml at 30 min[16]
in Kangro breed of goats
(Capra Hircus) (2640 microgml at 20 min[10][50]
found after intramuscular administration of
ceforazone peak plasma concentration was (976 microgml) at 45min This result was also higher
than that recorded for ceftriaxone in buffalo calves (158 microgml)[13]
The calculated maximum serum concentration (Cmax) is (40015 microgml) at maximum time
(tmax) of 157 hours The reported (Cmax) agreed with the data reported for cefipime in goats
(4932 microgml[47]
The reported maximum serum concentration (Cmax) is higher than that
reported for ceftriaxone in lactating goats(236 microgml)[9]
in lactating ewes (1722 microgml[25]
in
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
goats (2151 microgml)[11]
for cefquinome in camels (123 microgml)[51]
for ceftriaxone in calves
(1534 microgml)[26]
in patanwadi sheep (1553 microgml)[8]
for cefpirome in cattle (101 microgml)[52]
And for ceftiofur in chickens (2594 μgml)[37]
On the other hand the result was lower than
that reported by[6]
who observed the maximum serum concentration (Cmax) of ceftriaxone in
human after ntramuscular administration was (805 microgml) also it was lower than that
reported for ceftriaxone in dog (11510 microgml)[53]
in domestic cats (5440 microgml)[15]
and for
ceftazoxime in goats (8878 microgml)[45]
The reported [tmax] is neerly similar to that reported for ceftriaxone (104hours)in lactating
ewes by[25]
On contrast it is longer than those reported for ceftriaxone in dogs
(129hours)[53]
for ceftriaxone in lactating goats (07hours)[9]
also the result was longer than
that reported for ceftriaxone in domestic cats (033hours)[15]
in buffulo calves (05 hours)[13]
and for cefpirome in cattle (075hours)[52]
The reported [tmax] is shorter than those reported
for cefquinome in camels (425hours)[51]
in sheep and goats (261 and 262 hours)[36]
and for
ceftiofur in chickens (251 hours)[37]
The elimination half life [t05(β)]
following a single intramuscular administration was 1804 hours This value is nearly agreed
with that recorded for cefquinomein camels (1024hours)[52]
On contrast this result is longer
than that reported for cephalexin in buffalo calves (243hours)[41]
for ceftriaxone in lactating
ewes (177hours)[25]
in buffalo calves (438hours)[13]
in goats (203 hours)[11]
and for
cefipime in goats (165 hours)[47]
The rate of total body clearance of ceftriaxone following a single intramuscular injection is
0043lkgh This value was lower than that reported for ceftriaxone in buffulo calves
(401Lkgh)[13]
in goats (304 Lkgh)[11]
and in sheep (222 Lkgh)[8]
Bioavailability is the fraction of the drug administered by non vascular rout that gains
accesses to the systemic circulation The obtained result revealed that the calculated systemic
bioavailability percent was 6128 It is equal to that recorded for cefpirome in cow calves
(61)[54]
It is nearly equal to that recorded for ceftriaxone in sheep (64)[8]
On the other
hand this value is higher than those recorded for cefperazone in crossbred calves (481)[50]
for ceftriaxone in goats (59)[11]
in calves (47)[55]
On contrast this value is lower than
those reported for cefotaxime in two cats 982 and 93)[57]
for cephradine in goats
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
(739)[58]
for ceftazidime in a rabbit (966)[27]
for ceftriaxone in lactating goats (85)[9]
in lactating ewes (836)[25]
in domestic cats 8572[15]
for cefipime in goats 8645[47]
for ceftriaxone in buffulo calves 702[13]
and for ceftiofur in chickens 8890[37]
Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium
infected goats twics dialy for five days revealed that the drug could be detected in a
therapeutic level for 12hours following repeated intramuscular administrations and exceeded
the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]
The relative higher serum concentrations of ceftriaxone after the last dose compared to the
first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12
hours intervals for five consecutive days These observations agreed with data reported by[36]
on comparing the data of serum levels of repeated intramuscular injections with first
intramuscular injection it was revealed that repeated intramuscular injections of cefquinome
have cumulative effect in both species sheep and goats
The obtained result is inconsistent with that reported by[56]
who found thatwhen cefotaxime
was administered repetitively in patients the ratio of maximal serum levels after the last dose
to those after the first dose demonstrated minimal accumulation of intact drug and by[60]
who
found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in
buffalo calves
The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium
infected goats are significantly lower than those in normal goats following repeated
intramuscular injection These lower blood concentrations in Salmonella typhimurium
infected goats might be attributed to the higher penetrating power of ceftriaxone to the
diseased tissues[48]
This phenomenon is similar to data recorded by[61]
who suggested that
Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of
ceftriaxone These alterations might be due to fever and inflammation induced by
infections[59]
proved that the serum concentrations of cephradine following intramuscular
administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after
each intramuscular dose with a lower significant values recorded in Escherichia-coli infected
goats than in normal goatsAlso similer to that reported by[62]
who observed that the
maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep
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1451
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
in comparison to normal sheepOn contrast[43]
reported that peak plasma level of cefotaxime
in febrile buffalo calves was higher than healthy buffalo calves
In this study the total body clearance (CLtot) in normal goats are significantly lower than in
Salmonella typhimurium infected goats This result supported by[61]
and[63]
fever and
inflammation are cardinal features in bacterial infection which may in turn caused an
increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all
these could lead to increased in the rate at which the drug was delivered to both organs which
were important sites of drug excretion This might somewhat explain the increase in the total
body clearance in infected goats This result is differ than that reported by[64]
who observed
that the clearance of ceftriaxone was significantly reduced in infected mice than in non
infected animals
The highest concentrations of ceftriaxone in milk are recorded 4 hours after each
intramuscular injection with a significant lower value in Salmonella typhimurium infected
goats than in normal goats This might be attributed to accumulation of drug in the inflammed
tissues[48]
This result is similar to those reported by[6559]
who found that milk concentrations
of gentamicin and cephradine were significantly lower in infected goats and cattle than in
normal ones respectively
The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the
non-ionic passive diffusion principle[66]
reported that most drug cross-lipid membranes by
passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly
influenced by the physicochemical properties of the drug[6768]
Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum
ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the
physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]
Milk
contains substantially more lipid and less protein than serum and is slightly more acidic
Therefore drugs which tend to concentrated in milk are weak bases with low serum protein
binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide
and aminothiazole also possesses an hydroxytriazinone group as new and additional
ionization center[70]
these compounds are sufficiently lipid- soluble to be able to penetrate
tissues
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
The dose of ceftriaxone used in the present study induced therapeutically concentrations in
milk These concentrations suggested that ceftriaxone would be efficacious in treatment of
mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily
for 3-5 days
The study showed that the urine concentrations of ceftriaxone are greater than the concurrent
serum concentrations following intramuscular injection This observation is similar to those
reported in cows after cephapirin administrations[71]
In the present study urine concentrations of ceftriaxone increased with the repetition of
dosing This observation supported by[72]
after repeated intramuscular administrations of
ceftriaxone in healthy volunteeres
The mean peak urine concentrations of ceftriaxone were reached 2 hours after each
intramuscular injection The lower urine ceftriaxone concentrations in Salmonella
typhimurium infected goats than in normal goats might be attributed to the accumulation of
the drug in the inflamed tissues[48]
The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower
ratio in Salmonella typhimurium infected goats than in normal goats at different time of
sampling This indicates that glomerular filteration seemed to be the main pathway of
ceftriaxone elimination This observation supported by[59]
who found that the ratio between
cephradine clearance from blood of goats to creatinine clearance showed a marked decrease
in Escherichia-coli infected goats than in normal goats This indicated that glomerular
filteration seemed to be the main pathway of cephradine elimination with a limited rate of
tubular reabsorption
CONCLUSION
The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value
referred a better absorption of ceftriaxone from its site of intramuscular administration The
high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular
administrations suggested that ceftriaxone could be used for treatment of mastitis caused by
Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats
The high concentrations of ceftriaxone in urine after repeated intramuscular administrations
suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in
goats
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84(3) 483-9
43 Sharma SK Srivastava AK and Deore DM (2006) Effect of Ecoli
lipopolysaccharides ndashinduced fever on disposition pattern of cefotaxime in buffalo calves
Veterinarski Arhiv 76(6) 537-545
44 Baggot JD (1977) Priniciple of pharmacokinetics In principle of drug disposition in
domestic animals The physiological Basis of veterinary Clinical Pharmacology 1st ed
WB Saunders Co Philadelphi PA 168-179
45 Karmaker UK Datta BK Patra PH Prashant M Suman S Sar TK Chakaborty
AK and mandal KT (2011) Disposition kinetics of ceftizoxime in healthy and mastitic
goats after intravenous adminsteration Pharmacologyonline 3 935-946
46 Ringger NC Pearson EG Gronwall R Kohlepp S J (1996) Pharmacokinetics of
ceftriaxone in healthy horses Equine Vet J Nov 28(6) 476-9
47 Prawez S Raina R Dimitrova D panka NK Ahanger AA Verma PK (2010) The
pharmacokinetics of cefipime in goats following single dose iv and im adminsteration
Turk j vet Anima Sci 34(5) 427-431
48 Baggot JD (1980) Distribution of antimicrobial agents in normal and diseased animals
JAVMA 19(76) 1085-1090
49 Haddad N S Pedersoli W M Ravis W R Fazeli M H and Carson Jr R L (1985)
Pharmacokinetics of gentamicin at steady-state in ponies serum urine and endometrial
concentrations Am J Vet Res 46(6) 1268-1271
50 Gupta JK Chaudhary RK and Dumka VK (2008) Pharmacokinetics after single
intramuscuker adminsrerarion and in-vitro binding plasma protein of cefoprazone in cross
bred calves Veterinaski Arhiv 78(5) 441-448
51 Al Taher AY (2010) Pharmacokinetics of cefquinome in camels J An Vet Ad 9(4)
848-852
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52 Rajput N Dumka V K and Sandhu HS (2012) Pharmacokinetics and in- vitro
plasma protein binding of cefpirome in cattle Veterinaski Arhiv 82(1) 1-9
53 RebueltoM Albarellos G Ambros L Kreil V Montoya L Bonafine R Otero P
Hallu R (2002) Pharmacokinetics of ceftriaxone administered by the intravenous
intramuscular or subcutaneous routes to dogs J Vet Pharmacol Ther Feb 25(1) 73-6
54 Patel RB Bhavsar SK Solanki PF Patel JH Varia RD Modi Falguni D and
Patel MD (2013) Pharmacokinetics of cefpirome following intravenous and
intramuscular administration in cow calves Sci Int 1(11) 371-374
55 Maradiya J J Goriya H V Bhavsar S K Patel U D and Thaker A M (2010)
Pharmacokinetics of ceftriaxone in calves Veterinarski arhiv 80(1) 1-9
56 Inges R MJ Fillastre J Godin M Leroy A and Humbert G (1982) The
Pharmacokinetics of cefotaxime and its metabolites in subjects with normal and impaired
renal function Clin Infect Dis (4) 379-391
57 Mcelroy D Ravis W R and Clark C H (1986) Pharmacokinetics of cefotaxime in
the domestic cats Am J Vet Res 47(1) 86-88
58 El-Sayed MG Atef M and El-Komy AA (1994) Disposition kinetic of cephradine in
normal and Escherichia coli infected goats Dtsch Tierarztl Wochenschr 101(2) 56-60
59 Soback S and Ziv G (1988) Pharmacokinetics and bioavailability of ceftriaxone
administered intravenously and intramuscularly to calves Am J Vet Res 49 535-538
60 Sharma S K and Srivastava A K (2003) Cefotaxime pharmacokinetics in male
buffalo calves following multiple dosing Veterinarski arhiv 73(4) 191-197
61 Abdulgafar O J Shaibu O B and Emmanuel U E (2011) Effect of Salmonella
typhymurium infection on the pharmacokinetics of ceftriaxone in sokoto red goats Niger
J Basic Applied Sci 19(1) 49-54
62 Ranjan R Birendra K R Amita R and Sanjeet K S (2011) Effect of Effect of E coli E
coli endotoxin induced fever on the pharmacokinetic profile and dosage regimen of
ceftriaxone in sheep (Ovis aries) Veterinarski arhiv 81(4) 423-432
63 Etuk EU and Onyeyili PA (2006) The effect of Salmonella infection on the plasma
kinetic of chloramphenicol in the sokoto red goats Inter J Pharmacol 2(1) 28-32
64 Wang E Bergeron Y and Bergeron MG (2005) Ceftriaxone pharmacokinetics in
interleukin-10-treated murine pneumococcal pneumonia J Antimicrob Chemother 55
721ndash726
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
65 El-Sayed MG Hatem ME and El-Komy AA (1989) Disposition kinetic of
gentamicin in normal and endometric cow using microbiological assay Dtsch Tierarztl
Wochenschr 96(8) 412-415
66 Aramyona JJ Mora J Fraile LJ Garcia MA Abadia AR and Breganate MA
(1996) Penetration of enrofloxacin and ciprofloxacin into breast milk and
pharmacokinetics of the drugs in lacating rabbits and neonatal offspring Am J Vet Res
57(4) 547-553
67 Rusmussen F (1966) Studies on the mammary excretion and absorbtion of drugs Vet
Rec (87) 14-18
68 Alkinson A and Begg E (1990) Prediction of drug distribution into human milk from
physicochemical characteristics Clin Pharmacokinet 18(2) 151-167
69 Kenneth F (1997) Drug distribution in human milk Aust Prescr 20(2) 35-40
70 Aleksić M Savić V Popović G Burić N and Kapetanović V (2005) Acidity
constants of cefetamet cefotaxime and ceftriaxone the effect of the substituent at C3
position J Pharm Biomed Anal 39(3-4) 752-756
71 Prades M Brown M P Gronwall R and Miles N S (1988) Pharmacokinetics of
sodium cephapirin in lactating dairy cows Am J Vet Res 49(11) 1888-1890
72 Holazo A A Patel I H Weinfeld R E Konikoff J J and Parsonnet M (1986)
Ceftriaxone pharmacokinetics following multiple intramuscular dosing Euro J Clin
Pharmacol 30(1) 109-112
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
In the present investigation the intravenous injection of 20 mg ceftriaxonekgbwt In normal
goats showed that the drug disposition best fitted a two-compartments- open model a
compartment of plasma and rapid equilibrating tissues and a deeper slower compartment
The obtained result is consistent with those reported for ceftriaxone in lactating goats[9]
lactating ewe[25]
domestic cat[15]
calves[26]
and patanwadi sheep[8]
Also this phenomenon is
in agreement with those reported for other cephalosporines as ceftazidime in a rabbit[27]
cefepime in dog and neonatal foals[28]
ewes[29]
ceftriaxone in goats[9]
cefipime in calves[30]
ceftiofur in cross-bred friesian cattle[31]
cefipime in calves[32]
ceftiofur in cows[33]
cefpirome
in cross-bred calves[3]
cefazidime in goats[35]
and cefquinome in sheep and goats[36]
cefipime
in chickens[37]
Ceftriaxone was distributed after intravenous injection with a distribution phase (α) equal to
656 per hour with a short distribution half ndash life [t05 (α)] equal to 0104 hour The shorter
distribution half-life of ceftriaxone in goats suggested the rapid distribution of the drug in
body tissue and fluid and that nearly similar to that recorded for ceftriaxone in lactating
goats(012 hour)[9]
for ceftriaxone in lactating ewes (0152 hour)[2]
and for ceftriaxone in
calves( 013hour)[26]
The rapid distribution of ceftriaxone in goats is supported by high rate constant of transfer of
the drug from central to peripheral compartment [K12 = 353 h-1
] as compared to the rate
constant of transfer of the drug from peripheral to central compartment [K21= 295 h-1
] This
value is nearly similar to those reported for cefotaxime in goats (K21=327 h-1
)[38]
On contrast
this value was higher than those recorded for ceftriaxone in lactating goats (K21=143 h-1
)[9]
in
lactating ewes (K21=125 h-1
)[25]
and in domestic cats (K21=154 h-1
)[15]
The apparent volume of distribution of ceftriaxone was (0355plusmn0004LKg) this value is
nearly similar to that recorded for cefaronide in sheep(039 LKg)[7]
cefotaxime in dog (048
lkg)[39]
in goat (051 lkg)
[40] for caphalexin in buffalo calves (041 Lkg)
[41] for cefipime in
ewes and calves (032 lkg) (043Lkg)[29]
and[30]
respectively For ceftriaxone in domestic
cats (057Lkg)[15]
in camel (032Lkg)[42]
On the other hand this result is differ than that
reported for cefotaxime in buffalo calves (117Lkg)[43]
High value of the volume of
distribution suggested extensive penetration power Drug with volume of distribution greater
than one literkilogram indicated wide distribution or extensive tissue binding or both[44]
The
apparent volume of distribution in the present study indicated moderate tissue penetrating
power This result agreed with[15]
for ceftriaxone in domestic cats
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1448
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
Ceftriaxone is eliminated in the current study following a single intravenous injection with
elimination half ndashlife [t 05(β)] equal to 519 hours This observation is nearly agreed with the
data recorded for ceftizoxime in goats (624hours)[45]
On contrast this value was longer than
that reported for ceftriaxone in lactating ewe (175hours)[25]
for cefaronide in sheep (17
hours)[7]
For cephalexin in buffulo calves (216hours)[41]
for ceftriaxone in healthy horse
(162hours)[46]
also this value is longer than that recorded for ceftriaxone in lactating goats
(144hours)[9]
for cefipime in goats (186hours)[47]
The rate of total body clearance of ceftriaxone following a single intravenous injection is
0048 lkgh which equal to data reported for ceftizoxime in lactating goats (005Lkgh)[45]
On contrast this value is lower than that reported for ceftriaxone in buffulo calves lactating
goats buffulo calves (Bubalus bubalis) goats (capra hircus) patanwadi sheep (026 Lkgh)
(395 Lkgh) (440 Lkgh) (450 Lkgh) (391 Lkgh)[12913118]
respectively
The variation in total body clearance might be attributed to specific interspecies variation
handling of the drug method used healthy status of the animal[48]
The difference between values calculated for pharmacokinetic parameters may be attributed
to animal species the drug formulation employed the age the size or sex o l lf the animal
or even inter individual variation and also due to method of analysis of the drug[49]
Following a single intramuscular injection of 20 mg ceftriaxonekg bwt In normal goats the
drug reached its peak serum concentrations after one hour of injection with value
of(41μgml) Ceftriaxone could be detected in serum in a therapeutic level (263μgml) at 12
hours post-injection The reported peak serum concentrations neerly similar to that reported
for cephalexin in buffulo calves (457 microgml)[41]
These results is differed than those reported
for ceftriaxone in cross breed calves (188 microgml at 30 min[16]
in Kangro breed of goats
(Capra Hircus) (2640 microgml at 20 min[10][50]
found after intramuscular administration of
ceforazone peak plasma concentration was (976 microgml) at 45min This result was also higher
than that recorded for ceftriaxone in buffalo calves (158 microgml)[13]
The calculated maximum serum concentration (Cmax) is (40015 microgml) at maximum time
(tmax) of 157 hours The reported (Cmax) agreed with the data reported for cefipime in goats
(4932 microgml[47]
The reported maximum serum concentration (Cmax) is higher than that
reported for ceftriaxone in lactating goats(236 microgml)[9]
in lactating ewes (1722 microgml[25]
in
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
goats (2151 microgml)[11]
for cefquinome in camels (123 microgml)[51]
for ceftriaxone in calves
(1534 microgml)[26]
in patanwadi sheep (1553 microgml)[8]
for cefpirome in cattle (101 microgml)[52]
And for ceftiofur in chickens (2594 μgml)[37]
On the other hand the result was lower than
that reported by[6]
who observed the maximum serum concentration (Cmax) of ceftriaxone in
human after ntramuscular administration was (805 microgml) also it was lower than that
reported for ceftriaxone in dog (11510 microgml)[53]
in domestic cats (5440 microgml)[15]
and for
ceftazoxime in goats (8878 microgml)[45]
The reported [tmax] is neerly similar to that reported for ceftriaxone (104hours)in lactating
ewes by[25]
On contrast it is longer than those reported for ceftriaxone in dogs
(129hours)[53]
for ceftriaxone in lactating goats (07hours)[9]
also the result was longer than
that reported for ceftriaxone in domestic cats (033hours)[15]
in buffulo calves (05 hours)[13]
and for cefpirome in cattle (075hours)[52]
The reported [tmax] is shorter than those reported
for cefquinome in camels (425hours)[51]
in sheep and goats (261 and 262 hours)[36]
and for
ceftiofur in chickens (251 hours)[37]
The elimination half life [t05(β)]
following a single intramuscular administration was 1804 hours This value is nearly agreed
with that recorded for cefquinomein camels (1024hours)[52]
On contrast this result is longer
than that reported for cephalexin in buffalo calves (243hours)[41]
for ceftriaxone in lactating
ewes (177hours)[25]
in buffalo calves (438hours)[13]
in goats (203 hours)[11]
and for
cefipime in goats (165 hours)[47]
The rate of total body clearance of ceftriaxone following a single intramuscular injection is
0043lkgh This value was lower than that reported for ceftriaxone in buffulo calves
(401Lkgh)[13]
in goats (304 Lkgh)[11]
and in sheep (222 Lkgh)[8]
Bioavailability is the fraction of the drug administered by non vascular rout that gains
accesses to the systemic circulation The obtained result revealed that the calculated systemic
bioavailability percent was 6128 It is equal to that recorded for cefpirome in cow calves
(61)[54]
It is nearly equal to that recorded for ceftriaxone in sheep (64)[8]
On the other
hand this value is higher than those recorded for cefperazone in crossbred calves (481)[50]
for ceftriaxone in goats (59)[11]
in calves (47)[55]
On contrast this value is lower than
those reported for cefotaxime in two cats 982 and 93)[57]
for cephradine in goats
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1450
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
(739)[58]
for ceftazidime in a rabbit (966)[27]
for ceftriaxone in lactating goats (85)[9]
in lactating ewes (836)[25]
in domestic cats 8572[15]
for cefipime in goats 8645[47]
for ceftriaxone in buffulo calves 702[13]
and for ceftiofur in chickens 8890[37]
Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium
infected goats twics dialy for five days revealed that the drug could be detected in a
therapeutic level for 12hours following repeated intramuscular administrations and exceeded
the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]
The relative higher serum concentrations of ceftriaxone after the last dose compared to the
first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12
hours intervals for five consecutive days These observations agreed with data reported by[36]
on comparing the data of serum levels of repeated intramuscular injections with first
intramuscular injection it was revealed that repeated intramuscular injections of cefquinome
have cumulative effect in both species sheep and goats
The obtained result is inconsistent with that reported by[56]
who found thatwhen cefotaxime
was administered repetitively in patients the ratio of maximal serum levels after the last dose
to those after the first dose demonstrated minimal accumulation of intact drug and by[60]
who
found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in
buffalo calves
The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium
infected goats are significantly lower than those in normal goats following repeated
intramuscular injection These lower blood concentrations in Salmonella typhimurium
infected goats might be attributed to the higher penetrating power of ceftriaxone to the
diseased tissues[48]
This phenomenon is similar to data recorded by[61]
who suggested that
Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of
ceftriaxone These alterations might be due to fever and inflammation induced by
infections[59]
proved that the serum concentrations of cephradine following intramuscular
administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after
each intramuscular dose with a lower significant values recorded in Escherichia-coli infected
goats than in normal goatsAlso similer to that reported by[62]
who observed that the
maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep
wwwwjppscom Vol 5 Issue 01 2016
1451
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
in comparison to normal sheepOn contrast[43]
reported that peak plasma level of cefotaxime
in febrile buffalo calves was higher than healthy buffalo calves
In this study the total body clearance (CLtot) in normal goats are significantly lower than in
Salmonella typhimurium infected goats This result supported by[61]
and[63]
fever and
inflammation are cardinal features in bacterial infection which may in turn caused an
increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all
these could lead to increased in the rate at which the drug was delivered to both organs which
were important sites of drug excretion This might somewhat explain the increase in the total
body clearance in infected goats This result is differ than that reported by[64]
who observed
that the clearance of ceftriaxone was significantly reduced in infected mice than in non
infected animals
The highest concentrations of ceftriaxone in milk are recorded 4 hours after each
intramuscular injection with a significant lower value in Salmonella typhimurium infected
goats than in normal goats This might be attributed to accumulation of drug in the inflammed
tissues[48]
This result is similar to those reported by[6559]
who found that milk concentrations
of gentamicin and cephradine were significantly lower in infected goats and cattle than in
normal ones respectively
The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the
non-ionic passive diffusion principle[66]
reported that most drug cross-lipid membranes by
passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly
influenced by the physicochemical properties of the drug[6768]
Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum
ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the
physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]
Milk
contains substantially more lipid and less protein than serum and is slightly more acidic
Therefore drugs which tend to concentrated in milk are weak bases with low serum protein
binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide
and aminothiazole also possesses an hydroxytriazinone group as new and additional
ionization center[70]
these compounds are sufficiently lipid- soluble to be able to penetrate
tissues
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
The dose of ceftriaxone used in the present study induced therapeutically concentrations in
milk These concentrations suggested that ceftriaxone would be efficacious in treatment of
mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily
for 3-5 days
The study showed that the urine concentrations of ceftriaxone are greater than the concurrent
serum concentrations following intramuscular injection This observation is similar to those
reported in cows after cephapirin administrations[71]
In the present study urine concentrations of ceftriaxone increased with the repetition of
dosing This observation supported by[72]
after repeated intramuscular administrations of
ceftriaxone in healthy volunteeres
The mean peak urine concentrations of ceftriaxone were reached 2 hours after each
intramuscular injection The lower urine ceftriaxone concentrations in Salmonella
typhimurium infected goats than in normal goats might be attributed to the accumulation of
the drug in the inflamed tissues[48]
The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower
ratio in Salmonella typhimurium infected goats than in normal goats at different time of
sampling This indicates that glomerular filteration seemed to be the main pathway of
ceftriaxone elimination This observation supported by[59]
who found that the ratio between
cephradine clearance from blood of goats to creatinine clearance showed a marked decrease
in Escherichia-coli infected goats than in normal goats This indicated that glomerular
filteration seemed to be the main pathway of cephradine elimination with a limited rate of
tubular reabsorption
CONCLUSION
The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value
referred a better absorption of ceftriaxone from its site of intramuscular administration The
high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular
administrations suggested that ceftriaxone could be used for treatment of mastitis caused by
Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats
The high concentrations of ceftriaxone in urine after repeated intramuscular administrations
suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections
wwwwjppscom Vol 5 Issue 01 2016
1453
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in
goats
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39 Guerrini HV English BP Filippich J L Schneider J and Bourne D W (1986)
The pharmacokinetics of cefotaxime in dog Vet Rec 119(4) 81-83
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40 Atef M Ramadan A Afifi N A and Youssef S A (1990) pharmacokinetic profile
of cefotaxime in goat Res Vet Sci 49(1) 34-38
41 Satish K G Chaudhary RK Srivastiva AK and Garg BD (1990) Pharmacokintics
and dosage regemine of cephalexine in buffulo calves (Bubalis Bubalis following single
intravenous and intramusculer adminsteration Veterinary research commuincation 14
59-62
42 Goudah A (2008) Pharmacokinetic parameters of ceftriaxone after single intravenous
and intramuscular administration in camels (Camelus Dromedarius) Res Vet Sci Jun
84(3) 483-9
43 Sharma SK Srivastava AK and Deore DM (2006) Effect of Ecoli
lipopolysaccharides ndashinduced fever on disposition pattern of cefotaxime in buffalo calves
Veterinarski Arhiv 76(6) 537-545
44 Baggot JD (1977) Priniciple of pharmacokinetics In principle of drug disposition in
domestic animals The physiological Basis of veterinary Clinical Pharmacology 1st ed
WB Saunders Co Philadelphi PA 168-179
45 Karmaker UK Datta BK Patra PH Prashant M Suman S Sar TK Chakaborty
AK and mandal KT (2011) Disposition kinetics of ceftizoxime in healthy and mastitic
goats after intravenous adminsteration Pharmacologyonline 3 935-946
46 Ringger NC Pearson EG Gronwall R Kohlepp S J (1996) Pharmacokinetics of
ceftriaxone in healthy horses Equine Vet J Nov 28(6) 476-9
47 Prawez S Raina R Dimitrova D panka NK Ahanger AA Verma PK (2010) The
pharmacokinetics of cefipime in goats following single dose iv and im adminsteration
Turk j vet Anima Sci 34(5) 427-431
48 Baggot JD (1980) Distribution of antimicrobial agents in normal and diseased animals
JAVMA 19(76) 1085-1090
49 Haddad N S Pedersoli W M Ravis W R Fazeli M H and Carson Jr R L (1985)
Pharmacokinetics of gentamicin at steady-state in ponies serum urine and endometrial
concentrations Am J Vet Res 46(6) 1268-1271
50 Gupta JK Chaudhary RK and Dumka VK (2008) Pharmacokinetics after single
intramuscuker adminsrerarion and in-vitro binding plasma protein of cefoprazone in cross
bred calves Veterinaski Arhiv 78(5) 441-448
51 Al Taher AY (2010) Pharmacokinetics of cefquinome in camels J An Vet Ad 9(4)
848-852
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52 Rajput N Dumka V K and Sandhu HS (2012) Pharmacokinetics and in- vitro
plasma protein binding of cefpirome in cattle Veterinaski Arhiv 82(1) 1-9
53 RebueltoM Albarellos G Ambros L Kreil V Montoya L Bonafine R Otero P
Hallu R (2002) Pharmacokinetics of ceftriaxone administered by the intravenous
intramuscular or subcutaneous routes to dogs J Vet Pharmacol Ther Feb 25(1) 73-6
54 Patel RB Bhavsar SK Solanki PF Patel JH Varia RD Modi Falguni D and
Patel MD (2013) Pharmacokinetics of cefpirome following intravenous and
intramuscular administration in cow calves Sci Int 1(11) 371-374
55 Maradiya J J Goriya H V Bhavsar S K Patel U D and Thaker A M (2010)
Pharmacokinetics of ceftriaxone in calves Veterinarski arhiv 80(1) 1-9
56 Inges R MJ Fillastre J Godin M Leroy A and Humbert G (1982) The
Pharmacokinetics of cefotaxime and its metabolites in subjects with normal and impaired
renal function Clin Infect Dis (4) 379-391
57 Mcelroy D Ravis W R and Clark C H (1986) Pharmacokinetics of cefotaxime in
the domestic cats Am J Vet Res 47(1) 86-88
58 El-Sayed MG Atef M and El-Komy AA (1994) Disposition kinetic of cephradine in
normal and Escherichia coli infected goats Dtsch Tierarztl Wochenschr 101(2) 56-60
59 Soback S and Ziv G (1988) Pharmacokinetics and bioavailability of ceftriaxone
administered intravenously and intramuscularly to calves Am J Vet Res 49 535-538
60 Sharma S K and Srivastava A K (2003) Cefotaxime pharmacokinetics in male
buffalo calves following multiple dosing Veterinarski arhiv 73(4) 191-197
61 Abdulgafar O J Shaibu O B and Emmanuel U E (2011) Effect of Salmonella
typhymurium infection on the pharmacokinetics of ceftriaxone in sokoto red goats Niger
J Basic Applied Sci 19(1) 49-54
62 Ranjan R Birendra K R Amita R and Sanjeet K S (2011) Effect of Effect of E coli E
coli endotoxin induced fever on the pharmacokinetic profile and dosage regimen of
ceftriaxone in sheep (Ovis aries) Veterinarski arhiv 81(4) 423-432
63 Etuk EU and Onyeyili PA (2006) The effect of Salmonella infection on the plasma
kinetic of chloramphenicol in the sokoto red goats Inter J Pharmacol 2(1) 28-32
64 Wang E Bergeron Y and Bergeron MG (2005) Ceftriaxone pharmacokinetics in
interleukin-10-treated murine pneumococcal pneumonia J Antimicrob Chemother 55
721ndash726
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
65 El-Sayed MG Hatem ME and El-Komy AA (1989) Disposition kinetic of
gentamicin in normal and endometric cow using microbiological assay Dtsch Tierarztl
Wochenschr 96(8) 412-415
66 Aramyona JJ Mora J Fraile LJ Garcia MA Abadia AR and Breganate MA
(1996) Penetration of enrofloxacin and ciprofloxacin into breast milk and
pharmacokinetics of the drugs in lacating rabbits and neonatal offspring Am J Vet Res
57(4) 547-553
67 Rusmussen F (1966) Studies on the mammary excretion and absorbtion of drugs Vet
Rec (87) 14-18
68 Alkinson A and Begg E (1990) Prediction of drug distribution into human milk from
physicochemical characteristics Clin Pharmacokinet 18(2) 151-167
69 Kenneth F (1997) Drug distribution in human milk Aust Prescr 20(2) 35-40
70 Aleksić M Savić V Popović G Burić N and Kapetanović V (2005) Acidity
constants of cefetamet cefotaxime and ceftriaxone the effect of the substituent at C3
position J Pharm Biomed Anal 39(3-4) 752-756
71 Prades M Brown M P Gronwall R and Miles N S (1988) Pharmacokinetics of
sodium cephapirin in lactating dairy cows Am J Vet Res 49(11) 1888-1890
72 Holazo A A Patel I H Weinfeld R E Konikoff J J and Parsonnet M (1986)
Ceftriaxone pharmacokinetics following multiple intramuscular dosing Euro J Clin
Pharmacol 30(1) 109-112
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
Ceftriaxone is eliminated in the current study following a single intravenous injection with
elimination half ndashlife [t 05(β)] equal to 519 hours This observation is nearly agreed with the
data recorded for ceftizoxime in goats (624hours)[45]
On contrast this value was longer than
that reported for ceftriaxone in lactating ewe (175hours)[25]
for cefaronide in sheep (17
hours)[7]
For cephalexin in buffulo calves (216hours)[41]
for ceftriaxone in healthy horse
(162hours)[46]
also this value is longer than that recorded for ceftriaxone in lactating goats
(144hours)[9]
for cefipime in goats (186hours)[47]
The rate of total body clearance of ceftriaxone following a single intravenous injection is
0048 lkgh which equal to data reported for ceftizoxime in lactating goats (005Lkgh)[45]
On contrast this value is lower than that reported for ceftriaxone in buffulo calves lactating
goats buffulo calves (Bubalus bubalis) goats (capra hircus) patanwadi sheep (026 Lkgh)
(395 Lkgh) (440 Lkgh) (450 Lkgh) (391 Lkgh)[12913118]
respectively
The variation in total body clearance might be attributed to specific interspecies variation
handling of the drug method used healthy status of the animal[48]
The difference between values calculated for pharmacokinetic parameters may be attributed
to animal species the drug formulation employed the age the size or sex o l lf the animal
or even inter individual variation and also due to method of analysis of the drug[49]
Following a single intramuscular injection of 20 mg ceftriaxonekg bwt In normal goats the
drug reached its peak serum concentrations after one hour of injection with value
of(41μgml) Ceftriaxone could be detected in serum in a therapeutic level (263μgml) at 12
hours post-injection The reported peak serum concentrations neerly similar to that reported
for cephalexin in buffulo calves (457 microgml)[41]
These results is differed than those reported
for ceftriaxone in cross breed calves (188 microgml at 30 min[16]
in Kangro breed of goats
(Capra Hircus) (2640 microgml at 20 min[10][50]
found after intramuscular administration of
ceforazone peak plasma concentration was (976 microgml) at 45min This result was also higher
than that recorded for ceftriaxone in buffalo calves (158 microgml)[13]
The calculated maximum serum concentration (Cmax) is (40015 microgml) at maximum time
(tmax) of 157 hours The reported (Cmax) agreed with the data reported for cefipime in goats
(4932 microgml[47]
The reported maximum serum concentration (Cmax) is higher than that
reported for ceftriaxone in lactating goats(236 microgml)[9]
in lactating ewes (1722 microgml[25]
in
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
goats (2151 microgml)[11]
for cefquinome in camels (123 microgml)[51]
for ceftriaxone in calves
(1534 microgml)[26]
in patanwadi sheep (1553 microgml)[8]
for cefpirome in cattle (101 microgml)[52]
And for ceftiofur in chickens (2594 μgml)[37]
On the other hand the result was lower than
that reported by[6]
who observed the maximum serum concentration (Cmax) of ceftriaxone in
human after ntramuscular administration was (805 microgml) also it was lower than that
reported for ceftriaxone in dog (11510 microgml)[53]
in domestic cats (5440 microgml)[15]
and for
ceftazoxime in goats (8878 microgml)[45]
The reported [tmax] is neerly similar to that reported for ceftriaxone (104hours)in lactating
ewes by[25]
On contrast it is longer than those reported for ceftriaxone in dogs
(129hours)[53]
for ceftriaxone in lactating goats (07hours)[9]
also the result was longer than
that reported for ceftriaxone in domestic cats (033hours)[15]
in buffulo calves (05 hours)[13]
and for cefpirome in cattle (075hours)[52]
The reported [tmax] is shorter than those reported
for cefquinome in camels (425hours)[51]
in sheep and goats (261 and 262 hours)[36]
and for
ceftiofur in chickens (251 hours)[37]
The elimination half life [t05(β)]
following a single intramuscular administration was 1804 hours This value is nearly agreed
with that recorded for cefquinomein camels (1024hours)[52]
On contrast this result is longer
than that reported for cephalexin in buffalo calves (243hours)[41]
for ceftriaxone in lactating
ewes (177hours)[25]
in buffalo calves (438hours)[13]
in goats (203 hours)[11]
and for
cefipime in goats (165 hours)[47]
The rate of total body clearance of ceftriaxone following a single intramuscular injection is
0043lkgh This value was lower than that reported for ceftriaxone in buffulo calves
(401Lkgh)[13]
in goats (304 Lkgh)[11]
and in sheep (222 Lkgh)[8]
Bioavailability is the fraction of the drug administered by non vascular rout that gains
accesses to the systemic circulation The obtained result revealed that the calculated systemic
bioavailability percent was 6128 It is equal to that recorded for cefpirome in cow calves
(61)[54]
It is nearly equal to that recorded for ceftriaxone in sheep (64)[8]
On the other
hand this value is higher than those recorded for cefperazone in crossbred calves (481)[50]
for ceftriaxone in goats (59)[11]
in calves (47)[55]
On contrast this value is lower than
those reported for cefotaxime in two cats 982 and 93)[57]
for cephradine in goats
wwwwjppscom Vol 5 Issue 01 2016
1450
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
(739)[58]
for ceftazidime in a rabbit (966)[27]
for ceftriaxone in lactating goats (85)[9]
in lactating ewes (836)[25]
in domestic cats 8572[15]
for cefipime in goats 8645[47]
for ceftriaxone in buffulo calves 702[13]
and for ceftiofur in chickens 8890[37]
Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium
infected goats twics dialy for five days revealed that the drug could be detected in a
therapeutic level for 12hours following repeated intramuscular administrations and exceeded
the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]
The relative higher serum concentrations of ceftriaxone after the last dose compared to the
first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12
hours intervals for five consecutive days These observations agreed with data reported by[36]
on comparing the data of serum levels of repeated intramuscular injections with first
intramuscular injection it was revealed that repeated intramuscular injections of cefquinome
have cumulative effect in both species sheep and goats
The obtained result is inconsistent with that reported by[56]
who found thatwhen cefotaxime
was administered repetitively in patients the ratio of maximal serum levels after the last dose
to those after the first dose demonstrated minimal accumulation of intact drug and by[60]
who
found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in
buffalo calves
The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium
infected goats are significantly lower than those in normal goats following repeated
intramuscular injection These lower blood concentrations in Salmonella typhimurium
infected goats might be attributed to the higher penetrating power of ceftriaxone to the
diseased tissues[48]
This phenomenon is similar to data recorded by[61]
who suggested that
Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of
ceftriaxone These alterations might be due to fever and inflammation induced by
infections[59]
proved that the serum concentrations of cephradine following intramuscular
administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after
each intramuscular dose with a lower significant values recorded in Escherichia-coli infected
goats than in normal goatsAlso similer to that reported by[62]
who observed that the
maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep
wwwwjppscom Vol 5 Issue 01 2016
1451
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
in comparison to normal sheepOn contrast[43]
reported that peak plasma level of cefotaxime
in febrile buffalo calves was higher than healthy buffalo calves
In this study the total body clearance (CLtot) in normal goats are significantly lower than in
Salmonella typhimurium infected goats This result supported by[61]
and[63]
fever and
inflammation are cardinal features in bacterial infection which may in turn caused an
increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all
these could lead to increased in the rate at which the drug was delivered to both organs which
were important sites of drug excretion This might somewhat explain the increase in the total
body clearance in infected goats This result is differ than that reported by[64]
who observed
that the clearance of ceftriaxone was significantly reduced in infected mice than in non
infected animals
The highest concentrations of ceftriaxone in milk are recorded 4 hours after each
intramuscular injection with a significant lower value in Salmonella typhimurium infected
goats than in normal goats This might be attributed to accumulation of drug in the inflammed
tissues[48]
This result is similar to those reported by[6559]
who found that milk concentrations
of gentamicin and cephradine were significantly lower in infected goats and cattle than in
normal ones respectively
The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the
non-ionic passive diffusion principle[66]
reported that most drug cross-lipid membranes by
passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly
influenced by the physicochemical properties of the drug[6768]
Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum
ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the
physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]
Milk
contains substantially more lipid and less protein than serum and is slightly more acidic
Therefore drugs which tend to concentrated in milk are weak bases with low serum protein
binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide
and aminothiazole also possesses an hydroxytriazinone group as new and additional
ionization center[70]
these compounds are sufficiently lipid- soluble to be able to penetrate
tissues
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
The dose of ceftriaxone used in the present study induced therapeutically concentrations in
milk These concentrations suggested that ceftriaxone would be efficacious in treatment of
mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily
for 3-5 days
The study showed that the urine concentrations of ceftriaxone are greater than the concurrent
serum concentrations following intramuscular injection This observation is similar to those
reported in cows after cephapirin administrations[71]
In the present study urine concentrations of ceftriaxone increased with the repetition of
dosing This observation supported by[72]
after repeated intramuscular administrations of
ceftriaxone in healthy volunteeres
The mean peak urine concentrations of ceftriaxone were reached 2 hours after each
intramuscular injection The lower urine ceftriaxone concentrations in Salmonella
typhimurium infected goats than in normal goats might be attributed to the accumulation of
the drug in the inflamed tissues[48]
The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower
ratio in Salmonella typhimurium infected goats than in normal goats at different time of
sampling This indicates that glomerular filteration seemed to be the main pathway of
ceftriaxone elimination This observation supported by[59]
who found that the ratio between
cephradine clearance from blood of goats to creatinine clearance showed a marked decrease
in Escherichia-coli infected goats than in normal goats This indicated that glomerular
filteration seemed to be the main pathway of cephradine elimination with a limited rate of
tubular reabsorption
CONCLUSION
The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value
referred a better absorption of ceftriaxone from its site of intramuscular administration The
high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular
administrations suggested that ceftriaxone could be used for treatment of mastitis caused by
Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats
The high concentrations of ceftriaxone in urine after repeated intramuscular administrations
suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections
wwwwjppscom Vol 5 Issue 01 2016
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in
goats
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concentrations Am J Vet Res 46(6) 1268-1271
50 Gupta JK Chaudhary RK and Dumka VK (2008) Pharmacokinetics after single
intramuscuker adminsrerarion and in-vitro binding plasma protein of cefoprazone in cross
bred calves Veterinaski Arhiv 78(5) 441-448
51 Al Taher AY (2010) Pharmacokinetics of cefquinome in camels J An Vet Ad 9(4)
848-852
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
52 Rajput N Dumka V K and Sandhu HS (2012) Pharmacokinetics and in- vitro
plasma protein binding of cefpirome in cattle Veterinaski Arhiv 82(1) 1-9
53 RebueltoM Albarellos G Ambros L Kreil V Montoya L Bonafine R Otero P
Hallu R (2002) Pharmacokinetics of ceftriaxone administered by the intravenous
intramuscular or subcutaneous routes to dogs J Vet Pharmacol Ther Feb 25(1) 73-6
54 Patel RB Bhavsar SK Solanki PF Patel JH Varia RD Modi Falguni D and
Patel MD (2013) Pharmacokinetics of cefpirome following intravenous and
intramuscular administration in cow calves Sci Int 1(11) 371-374
55 Maradiya J J Goriya H V Bhavsar S K Patel U D and Thaker A M (2010)
Pharmacokinetics of ceftriaxone in calves Veterinarski arhiv 80(1) 1-9
56 Inges R MJ Fillastre J Godin M Leroy A and Humbert G (1982) The
Pharmacokinetics of cefotaxime and its metabolites in subjects with normal and impaired
renal function Clin Infect Dis (4) 379-391
57 Mcelroy D Ravis W R and Clark C H (1986) Pharmacokinetics of cefotaxime in
the domestic cats Am J Vet Res 47(1) 86-88
58 El-Sayed MG Atef M and El-Komy AA (1994) Disposition kinetic of cephradine in
normal and Escherichia coli infected goats Dtsch Tierarztl Wochenschr 101(2) 56-60
59 Soback S and Ziv G (1988) Pharmacokinetics and bioavailability of ceftriaxone
administered intravenously and intramuscularly to calves Am J Vet Res 49 535-538
60 Sharma S K and Srivastava A K (2003) Cefotaxime pharmacokinetics in male
buffalo calves following multiple dosing Veterinarski arhiv 73(4) 191-197
61 Abdulgafar O J Shaibu O B and Emmanuel U E (2011) Effect of Salmonella
typhymurium infection on the pharmacokinetics of ceftriaxone in sokoto red goats Niger
J Basic Applied Sci 19(1) 49-54
62 Ranjan R Birendra K R Amita R and Sanjeet K S (2011) Effect of Effect of E coli E
coli endotoxin induced fever on the pharmacokinetic profile and dosage regimen of
ceftriaxone in sheep (Ovis aries) Veterinarski arhiv 81(4) 423-432
63 Etuk EU and Onyeyili PA (2006) The effect of Salmonella infection on the plasma
kinetic of chloramphenicol in the sokoto red goats Inter J Pharmacol 2(1) 28-32
64 Wang E Bergeron Y and Bergeron MG (2005) Ceftriaxone pharmacokinetics in
interleukin-10-treated murine pneumococcal pneumonia J Antimicrob Chemother 55
721ndash726
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
65 El-Sayed MG Hatem ME and El-Komy AA (1989) Disposition kinetic of
gentamicin in normal and endometric cow using microbiological assay Dtsch Tierarztl
Wochenschr 96(8) 412-415
66 Aramyona JJ Mora J Fraile LJ Garcia MA Abadia AR and Breganate MA
(1996) Penetration of enrofloxacin and ciprofloxacin into breast milk and
pharmacokinetics of the drugs in lacating rabbits and neonatal offspring Am J Vet Res
57(4) 547-553
67 Rusmussen F (1966) Studies on the mammary excretion and absorbtion of drugs Vet
Rec (87) 14-18
68 Alkinson A and Begg E (1990) Prediction of drug distribution into human milk from
physicochemical characteristics Clin Pharmacokinet 18(2) 151-167
69 Kenneth F (1997) Drug distribution in human milk Aust Prescr 20(2) 35-40
70 Aleksić M Savić V Popović G Burić N and Kapetanović V (2005) Acidity
constants of cefetamet cefotaxime and ceftriaxone the effect of the substituent at C3
position J Pharm Biomed Anal 39(3-4) 752-756
71 Prades M Brown M P Gronwall R and Miles N S (1988) Pharmacokinetics of
sodium cephapirin in lactating dairy cows Am J Vet Res 49(11) 1888-1890
72 Holazo A A Patel I H Weinfeld R E Konikoff J J and Parsonnet M (1986)
Ceftriaxone pharmacokinetics following multiple intramuscular dosing Euro J Clin
Pharmacol 30(1) 109-112
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
goats (2151 microgml)[11]
for cefquinome in camels (123 microgml)[51]
for ceftriaxone in calves
(1534 microgml)[26]
in patanwadi sheep (1553 microgml)[8]
for cefpirome in cattle (101 microgml)[52]
And for ceftiofur in chickens (2594 μgml)[37]
On the other hand the result was lower than
that reported by[6]
who observed the maximum serum concentration (Cmax) of ceftriaxone in
human after ntramuscular administration was (805 microgml) also it was lower than that
reported for ceftriaxone in dog (11510 microgml)[53]
in domestic cats (5440 microgml)[15]
and for
ceftazoxime in goats (8878 microgml)[45]
The reported [tmax] is neerly similar to that reported for ceftriaxone (104hours)in lactating
ewes by[25]
On contrast it is longer than those reported for ceftriaxone in dogs
(129hours)[53]
for ceftriaxone in lactating goats (07hours)[9]
also the result was longer than
that reported for ceftriaxone in domestic cats (033hours)[15]
in buffulo calves (05 hours)[13]
and for cefpirome in cattle (075hours)[52]
The reported [tmax] is shorter than those reported
for cefquinome in camels (425hours)[51]
in sheep and goats (261 and 262 hours)[36]
and for
ceftiofur in chickens (251 hours)[37]
The elimination half life [t05(β)]
following a single intramuscular administration was 1804 hours This value is nearly agreed
with that recorded for cefquinomein camels (1024hours)[52]
On contrast this result is longer
than that reported for cephalexin in buffalo calves (243hours)[41]
for ceftriaxone in lactating
ewes (177hours)[25]
in buffalo calves (438hours)[13]
in goats (203 hours)[11]
and for
cefipime in goats (165 hours)[47]
The rate of total body clearance of ceftriaxone following a single intramuscular injection is
0043lkgh This value was lower than that reported for ceftriaxone in buffulo calves
(401Lkgh)[13]
in goats (304 Lkgh)[11]
and in sheep (222 Lkgh)[8]
Bioavailability is the fraction of the drug administered by non vascular rout that gains
accesses to the systemic circulation The obtained result revealed that the calculated systemic
bioavailability percent was 6128 It is equal to that recorded for cefpirome in cow calves
(61)[54]
It is nearly equal to that recorded for ceftriaxone in sheep (64)[8]
On the other
hand this value is higher than those recorded for cefperazone in crossbred calves (481)[50]
for ceftriaxone in goats (59)[11]
in calves (47)[55]
On contrast this value is lower than
those reported for cefotaxime in two cats 982 and 93)[57]
for cephradine in goats
wwwwjppscom Vol 5 Issue 01 2016
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
(739)[58]
for ceftazidime in a rabbit (966)[27]
for ceftriaxone in lactating goats (85)[9]
in lactating ewes (836)[25]
in domestic cats 8572[15]
for cefipime in goats 8645[47]
for ceftriaxone in buffulo calves 702[13]
and for ceftiofur in chickens 8890[37]
Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium
infected goats twics dialy for five days revealed that the drug could be detected in a
therapeutic level for 12hours following repeated intramuscular administrations and exceeded
the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]
The relative higher serum concentrations of ceftriaxone after the last dose compared to the
first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12
hours intervals for five consecutive days These observations agreed with data reported by[36]
on comparing the data of serum levels of repeated intramuscular injections with first
intramuscular injection it was revealed that repeated intramuscular injections of cefquinome
have cumulative effect in both species sheep and goats
The obtained result is inconsistent with that reported by[56]
who found thatwhen cefotaxime
was administered repetitively in patients the ratio of maximal serum levels after the last dose
to those after the first dose demonstrated minimal accumulation of intact drug and by[60]
who
found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in
buffalo calves
The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium
infected goats are significantly lower than those in normal goats following repeated
intramuscular injection These lower blood concentrations in Salmonella typhimurium
infected goats might be attributed to the higher penetrating power of ceftriaxone to the
diseased tissues[48]
This phenomenon is similar to data recorded by[61]
who suggested that
Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of
ceftriaxone These alterations might be due to fever and inflammation induced by
infections[59]
proved that the serum concentrations of cephradine following intramuscular
administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after
each intramuscular dose with a lower significant values recorded in Escherichia-coli infected
goats than in normal goatsAlso similer to that reported by[62]
who observed that the
maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep
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1451
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
in comparison to normal sheepOn contrast[43]
reported that peak plasma level of cefotaxime
in febrile buffalo calves was higher than healthy buffalo calves
In this study the total body clearance (CLtot) in normal goats are significantly lower than in
Salmonella typhimurium infected goats This result supported by[61]
and[63]
fever and
inflammation are cardinal features in bacterial infection which may in turn caused an
increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all
these could lead to increased in the rate at which the drug was delivered to both organs which
were important sites of drug excretion This might somewhat explain the increase in the total
body clearance in infected goats This result is differ than that reported by[64]
who observed
that the clearance of ceftriaxone was significantly reduced in infected mice than in non
infected animals
The highest concentrations of ceftriaxone in milk are recorded 4 hours after each
intramuscular injection with a significant lower value in Salmonella typhimurium infected
goats than in normal goats This might be attributed to accumulation of drug in the inflammed
tissues[48]
This result is similar to those reported by[6559]
who found that milk concentrations
of gentamicin and cephradine were significantly lower in infected goats and cattle than in
normal ones respectively
The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the
non-ionic passive diffusion principle[66]
reported that most drug cross-lipid membranes by
passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly
influenced by the physicochemical properties of the drug[6768]
Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum
ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the
physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]
Milk
contains substantially more lipid and less protein than serum and is slightly more acidic
Therefore drugs which tend to concentrated in milk are weak bases with low serum protein
binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide
and aminothiazole also possesses an hydroxytriazinone group as new and additional
ionization center[70]
these compounds are sufficiently lipid- soluble to be able to penetrate
tissues
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1452
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
The dose of ceftriaxone used in the present study induced therapeutically concentrations in
milk These concentrations suggested that ceftriaxone would be efficacious in treatment of
mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily
for 3-5 days
The study showed that the urine concentrations of ceftriaxone are greater than the concurrent
serum concentrations following intramuscular injection This observation is similar to those
reported in cows after cephapirin administrations[71]
In the present study urine concentrations of ceftriaxone increased with the repetition of
dosing This observation supported by[72]
after repeated intramuscular administrations of
ceftriaxone in healthy volunteeres
The mean peak urine concentrations of ceftriaxone were reached 2 hours after each
intramuscular injection The lower urine ceftriaxone concentrations in Salmonella
typhimurium infected goats than in normal goats might be attributed to the accumulation of
the drug in the inflamed tissues[48]
The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower
ratio in Salmonella typhimurium infected goats than in normal goats at different time of
sampling This indicates that glomerular filteration seemed to be the main pathway of
ceftriaxone elimination This observation supported by[59]
who found that the ratio between
cephradine clearance from blood of goats to creatinine clearance showed a marked decrease
in Escherichia-coli infected goats than in normal goats This indicated that glomerular
filteration seemed to be the main pathway of cephradine elimination with a limited rate of
tubular reabsorption
CONCLUSION
The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value
referred a better absorption of ceftriaxone from its site of intramuscular administration The
high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular
administrations suggested that ceftriaxone could be used for treatment of mastitis caused by
Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats
The high concentrations of ceftriaxone in urine after repeated intramuscular administrations
suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections
wwwwjppscom Vol 5 Issue 01 2016
1453
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in
goats
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2 Richard DM Heel RC Brogden RN Speight TM Avery GS (1984) Ceftriaxone a
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3 Brogden RN and Ward A (1988) Ceftriaxone a reappraisal of its antibacterial activity
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4 Waxman DJ and Strominger JL (1983) Penicillin-binding proteins and the
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5 Christ W (1991) properties of cephalosporines Infestion 19 244-252
6 Goonetilleke AK Dev D Aziz I Hughes C Smith MJ Basran GS (1996) A
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7 Guerrini VH Filippich LJ Cao G R English PB Bourne DW (1985)
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8 Swati Tiwari S Patel UD Bhavsar SK and Thaker AM (2010) Pharmacokinetics
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9 Ismail MM (2005) Pharmacokinetics urinary and mammary excretion of ceftriaxone in
lactating goats J Vet Med A Physiol Pathol Clin Med Sep 52(7) 354-8
10 Rajinder R prawez S Srivastiva AS (2005) Pharmacokinetics and dosage regimen of
ceftriaxone following its single ntramuscular adminsteration in kagani breed of goats
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11 Tiwari S Swati Bhavsar SK Patel UD and Thaker AM (2009) Disposition of
Ceftriaxone in Goats (Capra hircus) Online veterinary journal 4(2)
12 Dardi MS Sharma SK and Srivastava AK (2004) Pharmacokinetics and Dosage
regimen of ceftriaxone in buffalo calves Vet Res Commun 28 331-338
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13 Gohil P V Patel U D Bhavsar S K Thaker A M (2009) Pharmacokinetics of
ceftriaxone in buffalo calves (Bubalus bubalis) following intravenous and intramuscular
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14 Maradyia JJ Harshad VG Shaliesh KB Urvesh DP Aswin MT (2010)
Pharmacokinetics of ceftriaxone in calves Veterinarski arhiv 80(1) 1-9 2010
15 Albarellos GA Kreil VE Landoni MF (2007) Pharmacokinetics of ceftriaxone after
intravenous intramuscular and subcutaneous administration to domestic cats J Vet
Pharmacol Ther Aug 30(4) 345-52
16 Johal B and Srivastava AK (1998) Pharmacokinetics urinary excretion and dosage
regimen of ceftriaxone in Crossbred cow calves 68(10)
17 Otesile EB Ahmed G and Adetosoye AI (1990) Experimental infection of Red Sokoto
goats with Salmonella typhimurium Rev Eacutelev Meacuted Veacutet Pays trop 43(1) 49-53
18 Iroha I R Amadi E S Orji JO and Esimone C O (2008) In vitro evaluation of the
activity of colloidal silver concentrate against Pseudomonas aeruginosa isolated from
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19 Bennett JV Brodie JL Benner E and Kibry W (1966) Simplified accurate method
for antibiotic assay for clinical specimen Appl Microbial 14 170-175
20 Grove DC and Randall WA (1955) Assay methods of antibiotics Medical
encyclopedia New York 79(12) 259-32
21 Murray R (1984) Creatinin kaplane et al Clinc Chem Ther CV Mosby Co S Louis
Toronto Princeton 1261-1266 and 418
22 Baggot JD (1978a) Some aspect of clinical pharmacokinetics in veterinary medicine I J
Vet Pharm Ther 1 5-18
23 Baggot JD (1978b) Some aspect of clinical pharmacokinetics in veterinary medicine II
J Vet Pharm Ther 1 111-118
24 Snedecor GW and Cokran WG (1980) Statistical method 7th
Ed The Iowa state
university press Ames Iowa USA 39-63
25 Goudah A Shin HC Shim JH Abd El-Aty AM (2006) Characterization of the
relationship between serum and milk residu disposition of ceftriaxone in lactating ewe J
Vet Pharmacol Ther Aug 29(4) 307-12
26 Jayesh J M Harshad V G Shailesh K B Urvesh D P and Aswin M T (2010)
Pharmacokinetics of ceftriaxone in calves Veterinarski arshiv 80(1) 1-9
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27 Abd-El-Aty AM Goudah A and Abo E S K (2001) Pharmacokinetics
intramuscular bioavailability and tissue residue profiles of ceftazidime in a rabbit
model Dtsch Tierarztl Wochenschr 108(4) 168-171
28 Gardner S Y and Papich M G (2001) Comparison of cefepime pharmacokinetics in
neonatal foals and adult dogs J Vet Pharmacol Therap 24(3) 187-192
29 Ismail M (2005a) Pharmacokinetics of cefepime administered by iv and im routes to
ewes J Vet Pharmacol Therap 28(6) 499-503
30 Patel U D Bhavsar S K and Thaker A M (2006) Pharmacokinetics and dosage
regimen of cefepime following single dose intravenous administration in calves Iran J
Pharmacol Therapeut 5(2) 127-130
31 El-Gendy AAM Tohamy MA and Ismail M (2007) Comparative pharmacokinetic
and renal clearance study of ceftiofur in cross breed friesian and buffalo calves BS Vet
Med J 17(1) 69-77
32 Joshi B and Kumar Sharma S (2009) The pharmacokinetics of cefepime in E coli
lipopolysaccharide induced febrile buffalo calves Veterinarski arhiv 79(6) 523-530
33 Tohamy MA (2008) Pharmacokinetics of ceftiofur sodium administered concomitantly
with dipyrone in healthy and feverish cows J Egypt Soc Pharmacol Exp Ther 29(2)
10-15
34 Rajput N Kumar V D and Sandhu HS (2011) Pharmacokinetics and dosage
regimen of cefpirome in febrile cross-bred calves Iran J Pharmacol Ther 10(1) 17-20
35 Abo-El- Sooud K and Tohamy MA (2011) Comparative pharmacokinetics and milk
concentrations of ceftazidime in healthy and mastitic goats Insight Pharmaceut Sci
1(1) 11-17
36 El-Hewaity M Abd El Latif A Soliman A and Aboubakr M (2014) Comparative
pharmacokinetics of cefquinome (Cobactan 25) following repeated intramuscular
administrations in sheep and goats J Vet Med Doi 949642 1-5
37 El-Sayed M G A El-Komy A A A El barawy A M and Ibrahim D M A (2015)
Pharmacokinetics and tissue residues of ceftiofur in normal and Escherichia coli infected
chickens J Phys Pharm Adv 5(3) 574-582
38 Datta B Mandal TK and Chakraborty A K (2003) Pharmacokinetics of cefotaxime
in goats with experimentally induced kidney damage Ind J pharmacol (35) 173-176
39 Guerrini HV English BP Filippich J L Schneider J and Bourne D W (1986)
The pharmacokinetics of cefotaxime in dog Vet Rec 119(4) 81-83
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40 Atef M Ramadan A Afifi N A and Youssef S A (1990) pharmacokinetic profile
of cefotaxime in goat Res Vet Sci 49(1) 34-38
41 Satish K G Chaudhary RK Srivastiva AK and Garg BD (1990) Pharmacokintics
and dosage regemine of cephalexine in buffulo calves (Bubalis Bubalis following single
intravenous and intramusculer adminsteration Veterinary research commuincation 14
59-62
42 Goudah A (2008) Pharmacokinetic parameters of ceftriaxone after single intravenous
and intramuscular administration in camels (Camelus Dromedarius) Res Vet Sci Jun
84(3) 483-9
43 Sharma SK Srivastava AK and Deore DM (2006) Effect of Ecoli
lipopolysaccharides ndashinduced fever on disposition pattern of cefotaxime in buffalo calves
Veterinarski Arhiv 76(6) 537-545
44 Baggot JD (1977) Priniciple of pharmacokinetics In principle of drug disposition in
domestic animals The physiological Basis of veterinary Clinical Pharmacology 1st ed
WB Saunders Co Philadelphi PA 168-179
45 Karmaker UK Datta BK Patra PH Prashant M Suman S Sar TK Chakaborty
AK and mandal KT (2011) Disposition kinetics of ceftizoxime in healthy and mastitic
goats after intravenous adminsteration Pharmacologyonline 3 935-946
46 Ringger NC Pearson EG Gronwall R Kohlepp S J (1996) Pharmacokinetics of
ceftriaxone in healthy horses Equine Vet J Nov 28(6) 476-9
47 Prawez S Raina R Dimitrova D panka NK Ahanger AA Verma PK (2010) The
pharmacokinetics of cefipime in goats following single dose iv and im adminsteration
Turk j vet Anima Sci 34(5) 427-431
48 Baggot JD (1980) Distribution of antimicrobial agents in normal and diseased animals
JAVMA 19(76) 1085-1090
49 Haddad N S Pedersoli W M Ravis W R Fazeli M H and Carson Jr R L (1985)
Pharmacokinetics of gentamicin at steady-state in ponies serum urine and endometrial
concentrations Am J Vet Res 46(6) 1268-1271
50 Gupta JK Chaudhary RK and Dumka VK (2008) Pharmacokinetics after single
intramuscuker adminsrerarion and in-vitro binding plasma protein of cefoprazone in cross
bred calves Veterinaski Arhiv 78(5) 441-448
51 Al Taher AY (2010) Pharmacokinetics of cefquinome in camels J An Vet Ad 9(4)
848-852
wwwwjppscom Vol 5 Issue 01 2016
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
52 Rajput N Dumka V K and Sandhu HS (2012) Pharmacokinetics and in- vitro
plasma protein binding of cefpirome in cattle Veterinaski Arhiv 82(1) 1-9
53 RebueltoM Albarellos G Ambros L Kreil V Montoya L Bonafine R Otero P
Hallu R (2002) Pharmacokinetics of ceftriaxone administered by the intravenous
intramuscular or subcutaneous routes to dogs J Vet Pharmacol Ther Feb 25(1) 73-6
54 Patel RB Bhavsar SK Solanki PF Patel JH Varia RD Modi Falguni D and
Patel MD (2013) Pharmacokinetics of cefpirome following intravenous and
intramuscular administration in cow calves Sci Int 1(11) 371-374
55 Maradiya J J Goriya H V Bhavsar S K Patel U D and Thaker A M (2010)
Pharmacokinetics of ceftriaxone in calves Veterinarski arhiv 80(1) 1-9
56 Inges R MJ Fillastre J Godin M Leroy A and Humbert G (1982) The
Pharmacokinetics of cefotaxime and its metabolites in subjects with normal and impaired
renal function Clin Infect Dis (4) 379-391
57 Mcelroy D Ravis W R and Clark C H (1986) Pharmacokinetics of cefotaxime in
the domestic cats Am J Vet Res 47(1) 86-88
58 El-Sayed MG Atef M and El-Komy AA (1994) Disposition kinetic of cephradine in
normal and Escherichia coli infected goats Dtsch Tierarztl Wochenschr 101(2) 56-60
59 Soback S and Ziv G (1988) Pharmacokinetics and bioavailability of ceftriaxone
administered intravenously and intramuscularly to calves Am J Vet Res 49 535-538
60 Sharma S K and Srivastava A K (2003) Cefotaxime pharmacokinetics in male
buffalo calves following multiple dosing Veterinarski arhiv 73(4) 191-197
61 Abdulgafar O J Shaibu O B and Emmanuel U E (2011) Effect of Salmonella
typhymurium infection on the pharmacokinetics of ceftriaxone in sokoto red goats Niger
J Basic Applied Sci 19(1) 49-54
62 Ranjan R Birendra K R Amita R and Sanjeet K S (2011) Effect of Effect of E coli E
coli endotoxin induced fever on the pharmacokinetic profile and dosage regimen of
ceftriaxone in sheep (Ovis aries) Veterinarski arhiv 81(4) 423-432
63 Etuk EU and Onyeyili PA (2006) The effect of Salmonella infection on the plasma
kinetic of chloramphenicol in the sokoto red goats Inter J Pharmacol 2(1) 28-32
64 Wang E Bergeron Y and Bergeron MG (2005) Ceftriaxone pharmacokinetics in
interleukin-10-treated murine pneumococcal pneumonia J Antimicrob Chemother 55
721ndash726
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
65 El-Sayed MG Hatem ME and El-Komy AA (1989) Disposition kinetic of
gentamicin in normal and endometric cow using microbiological assay Dtsch Tierarztl
Wochenschr 96(8) 412-415
66 Aramyona JJ Mora J Fraile LJ Garcia MA Abadia AR and Breganate MA
(1996) Penetration of enrofloxacin and ciprofloxacin into breast milk and
pharmacokinetics of the drugs in lacating rabbits and neonatal offspring Am J Vet Res
57(4) 547-553
67 Rusmussen F (1966) Studies on the mammary excretion and absorbtion of drugs Vet
Rec (87) 14-18
68 Alkinson A and Begg E (1990) Prediction of drug distribution into human milk from
physicochemical characteristics Clin Pharmacokinet 18(2) 151-167
69 Kenneth F (1997) Drug distribution in human milk Aust Prescr 20(2) 35-40
70 Aleksić M Savić V Popović G Burić N and Kapetanović V (2005) Acidity
constants of cefetamet cefotaxime and ceftriaxone the effect of the substituent at C3
position J Pharm Biomed Anal 39(3-4) 752-756
71 Prades M Brown M P Gronwall R and Miles N S (1988) Pharmacokinetics of
sodium cephapirin in lactating dairy cows Am J Vet Res 49(11) 1888-1890
72 Holazo A A Patel I H Weinfeld R E Konikoff J J and Parsonnet M (1986)
Ceftriaxone pharmacokinetics following multiple intramuscular dosing Euro J Clin
Pharmacol 30(1) 109-112
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1450
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
(739)[58]
for ceftazidime in a rabbit (966)[27]
for ceftriaxone in lactating goats (85)[9]
in lactating ewes (836)[25]
in domestic cats 8572[15]
for cefipime in goats 8645[47]
for ceftriaxone in buffulo calves 702[13]
and for ceftiofur in chickens 8890[37]
Repeated intramusculer adminsteration of ceftriaxone in normal and Salmonella typhimurium
infected goats twics dialy for five days revealed that the drug could be detected in a
therapeutic level for 12hours following repeated intramuscular administrations and exceeded
the minimum inhibitory concentration(MIC90)of ceftriaxone(02mgml)[59]
The relative higher serum concentrations of ceftriaxone after the last dose compared to the
first doses indicated the accumulation of ceftriaxone in blood during multiple dosing at 12
hours intervals for five consecutive days These observations agreed with data reported by[36]
on comparing the data of serum levels of repeated intramuscular injections with first
intramuscular injection it was revealed that repeated intramuscular injections of cefquinome
have cumulative effect in both species sheep and goats
The obtained result is inconsistent with that reported by[56]
who found thatwhen cefotaxime
was administered repetitively in patients the ratio of maximal serum levels after the last dose
to those after the first dose demonstrated minimal accumulation of intact drug and by[60]
who
found that a lack of cumulative effect after repeated intramuscular injection of cefotaxime in
buffalo calves
The study showed that the blood concentrations of ceftriaxone in Salmonella typhimurium
infected goats are significantly lower than those in normal goats following repeated
intramuscular injection These lower blood concentrations in Salmonella typhimurium
infected goats might be attributed to the higher penetrating power of ceftriaxone to the
diseased tissues[48]
This phenomenon is similar to data recorded by[61]
who suggested that
Salmonella typhimurium infection in red sokoto goats significantly altered plasma kinetics of
ceftriaxone These alterations might be due to fever and inflammation induced by
infections[59]
proved that the serum concentrations of cephradine following intramuscular
administrations of 10 mgkg bwt Twice daily for five consecutive days peaked 2 hours after
each intramuscular dose with a lower significant values recorded in Escherichia-coli infected
goats than in normal goatsAlso similer to that reported by[62]
who observed that the
maximum plasma drug concentration of ceftriaxone was 1633 per cent lower in febrile sheep
wwwwjppscom Vol 5 Issue 01 2016
1451
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
in comparison to normal sheepOn contrast[43]
reported that peak plasma level of cefotaxime
in febrile buffalo calves was higher than healthy buffalo calves
In this study the total body clearance (CLtot) in normal goats are significantly lower than in
Salmonella typhimurium infected goats This result supported by[61]
and[63]
fever and
inflammation are cardinal features in bacterial infection which may in turn caused an
increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all
these could lead to increased in the rate at which the drug was delivered to both organs which
were important sites of drug excretion This might somewhat explain the increase in the total
body clearance in infected goats This result is differ than that reported by[64]
who observed
that the clearance of ceftriaxone was significantly reduced in infected mice than in non
infected animals
The highest concentrations of ceftriaxone in milk are recorded 4 hours after each
intramuscular injection with a significant lower value in Salmonella typhimurium infected
goats than in normal goats This might be attributed to accumulation of drug in the inflammed
tissues[48]
This result is similar to those reported by[6559]
who found that milk concentrations
of gentamicin and cephradine were significantly lower in infected goats and cattle than in
normal ones respectively
The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the
non-ionic passive diffusion principle[66]
reported that most drug cross-lipid membranes by
passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly
influenced by the physicochemical properties of the drug[6768]
Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum
ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the
physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]
Milk
contains substantially more lipid and less protein than serum and is slightly more acidic
Therefore drugs which tend to concentrated in milk are weak bases with low serum protein
binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide
and aminothiazole also possesses an hydroxytriazinone group as new and additional
ionization center[70]
these compounds are sufficiently lipid- soluble to be able to penetrate
tissues
wwwwjppscom Vol 5 Issue 01 2016
1452
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
The dose of ceftriaxone used in the present study induced therapeutically concentrations in
milk These concentrations suggested that ceftriaxone would be efficacious in treatment of
mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily
for 3-5 days
The study showed that the urine concentrations of ceftriaxone are greater than the concurrent
serum concentrations following intramuscular injection This observation is similar to those
reported in cows after cephapirin administrations[71]
In the present study urine concentrations of ceftriaxone increased with the repetition of
dosing This observation supported by[72]
after repeated intramuscular administrations of
ceftriaxone in healthy volunteeres
The mean peak urine concentrations of ceftriaxone were reached 2 hours after each
intramuscular injection The lower urine ceftriaxone concentrations in Salmonella
typhimurium infected goats than in normal goats might be attributed to the accumulation of
the drug in the inflamed tissues[48]
The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower
ratio in Salmonella typhimurium infected goats than in normal goats at different time of
sampling This indicates that glomerular filteration seemed to be the main pathway of
ceftriaxone elimination This observation supported by[59]
who found that the ratio between
cephradine clearance from blood of goats to creatinine clearance showed a marked decrease
in Escherichia-coli infected goats than in normal goats This indicated that glomerular
filteration seemed to be the main pathway of cephradine elimination with a limited rate of
tubular reabsorption
CONCLUSION
The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value
referred a better absorption of ceftriaxone from its site of intramuscular administration The
high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular
administrations suggested that ceftriaxone could be used for treatment of mastitis caused by
Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats
The high concentrations of ceftriaxone in urine after repeated intramuscular administrations
suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections
wwwwjppscom Vol 5 Issue 01 2016
1453
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in
goats
REFERANCES
1 Neu HC Merpol NJ and Fukp (1981) Antibacterial activity of ceftriaxone
abetalactamase stable cephalosporines Antimicrobial agents and chemotherapy 19
414-423
2 Richard DM Heel RC Brogden RN Speight TM Avery GS (1984) Ceftriaxone a
review of its antibacterial activity pharmacological properties and therapeutic uses
Drugs 27 469-527
3 Brogden RN and Ward A (1988) Ceftriaxone a reappraisal of its antibacterial activity
and pharmacokinetic properties and an update on its therapeutic use with particular
reference to once-daily administration Drugs 35 604-645
4 Waxman DJ and Strominger JL (1983) Penicillin-binding proteins and the
mechanism of action of beta-lactam antibiotics Annu Rev Biochem 52(1) 825-869
5 Christ W (1991) properties of cephalosporines Infestion 19 244-252
6 Goonetilleke AK Dev D Aziz I Hughes C Smith MJ Basran GS (1996) A
comparative analysis of pharmacokinetics of ceftriaxone in serum and pleural fluid in
humans a study of once daily administration by intramuscular intravenous routes J
Antimicrob Chemother Dec 38(6) 969-76
7 Guerrini VH Filippich LJ Cao G R English PB Bourne DW (1985)
Pharmacokinetics of cefaronide ceftriaxone and cefperazone in sheep J Vet Pharmacol
Ther 8(2) 120-7
8 Swati Tiwari S Patel UD Bhavsar SK and Thaker AM (2010) Pharmacokinetics
and Bioavailability of Ceftriaxone in Patanwadi Sheep Online veterinary journal 5(2)
9 Ismail MM (2005) Pharmacokinetics urinary and mammary excretion of ceftriaxone in
lactating goats J Vet Med A Physiol Pathol Clin Med Sep 52(7) 354-8
10 Rajinder R prawez S Srivastiva AS (2005) Pharmacokinetics and dosage regimen of
ceftriaxone following its single ntramuscular adminsteration in kagani breed of goats
(Capra Hircus) Journal of reaserch 4(2) 91-93
11 Tiwari S Swati Bhavsar SK Patel UD and Thaker AM (2009) Disposition of
Ceftriaxone in Goats (Capra hircus) Online veterinary journal 4(2)
12 Dardi MS Sharma SK and Srivastava AK (2004) Pharmacokinetics and Dosage
regimen of ceftriaxone in buffalo calves Vet Res Commun 28 331-338
wwwwjppscom Vol 5 Issue 01 2016
1454
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
13 Gohil P V Patel U D Bhavsar S K Thaker A M (2009) Pharmacokinetics of
ceftriaxone in buffalo calves (Bubalus bubalis) following intravenous and intramuscular
administration Iranian Journal of Veterinary Research 10(1) 33-37
14 Maradyia JJ Harshad VG Shaliesh KB Urvesh DP Aswin MT (2010)
Pharmacokinetics of ceftriaxone in calves Veterinarski arhiv 80(1) 1-9 2010
15 Albarellos GA Kreil VE Landoni MF (2007) Pharmacokinetics of ceftriaxone after
intravenous intramuscular and subcutaneous administration to domestic cats J Vet
Pharmacol Ther Aug 30(4) 345-52
16 Johal B and Srivastava AK (1998) Pharmacokinetics urinary excretion and dosage
regimen of ceftriaxone in Crossbred cow calves 68(10)
17 Otesile EB Ahmed G and Adetosoye AI (1990) Experimental infection of Red Sokoto
goats with Salmonella typhimurium Rev Eacutelev Meacuted Veacutet Pays trop 43(1) 49-53
18 Iroha I R Amadi E S Orji JO and Esimone C O (2008) In vitro evaluation of the
activity of colloidal silver concentrate against Pseudomonas aeruginosa isolated from
postoperative wound infection Scientific Research and Essay May 3(5) 209-211
19 Bennett JV Brodie JL Benner E and Kibry W (1966) Simplified accurate method
for antibiotic assay for clinical specimen Appl Microbial 14 170-175
20 Grove DC and Randall WA (1955) Assay methods of antibiotics Medical
encyclopedia New York 79(12) 259-32
21 Murray R (1984) Creatinin kaplane et al Clinc Chem Ther CV Mosby Co S Louis
Toronto Princeton 1261-1266 and 418
22 Baggot JD (1978a) Some aspect of clinical pharmacokinetics in veterinary medicine I J
Vet Pharm Ther 1 5-18
23 Baggot JD (1978b) Some aspect of clinical pharmacokinetics in veterinary medicine II
J Vet Pharm Ther 1 111-118
24 Snedecor GW and Cokran WG (1980) Statistical method 7th
Ed The Iowa state
university press Ames Iowa USA 39-63
25 Goudah A Shin HC Shim JH Abd El-Aty AM (2006) Characterization of the
relationship between serum and milk residu disposition of ceftriaxone in lactating ewe J
Vet Pharmacol Ther Aug 29(4) 307-12
26 Jayesh J M Harshad V G Shailesh K B Urvesh D P and Aswin M T (2010)
Pharmacokinetics of ceftriaxone in calves Veterinarski arshiv 80(1) 1-9
wwwwjppscom Vol 5 Issue 01 2016
1455
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
27 Abd-El-Aty AM Goudah A and Abo E S K (2001) Pharmacokinetics
intramuscular bioavailability and tissue residue profiles of ceftazidime in a rabbit
model Dtsch Tierarztl Wochenschr 108(4) 168-171
28 Gardner S Y and Papich M G (2001) Comparison of cefepime pharmacokinetics in
neonatal foals and adult dogs J Vet Pharmacol Therap 24(3) 187-192
29 Ismail M (2005a) Pharmacokinetics of cefepime administered by iv and im routes to
ewes J Vet Pharmacol Therap 28(6) 499-503
30 Patel U D Bhavsar S K and Thaker A M (2006) Pharmacokinetics and dosage
regimen of cefepime following single dose intravenous administration in calves Iran J
Pharmacol Therapeut 5(2) 127-130
31 El-Gendy AAM Tohamy MA and Ismail M (2007) Comparative pharmacokinetic
and renal clearance study of ceftiofur in cross breed friesian and buffalo calves BS Vet
Med J 17(1) 69-77
32 Joshi B and Kumar Sharma S (2009) The pharmacokinetics of cefepime in E coli
lipopolysaccharide induced febrile buffalo calves Veterinarski arhiv 79(6) 523-530
33 Tohamy MA (2008) Pharmacokinetics of ceftiofur sodium administered concomitantly
with dipyrone in healthy and feverish cows J Egypt Soc Pharmacol Exp Ther 29(2)
10-15
34 Rajput N Kumar V D and Sandhu HS (2011) Pharmacokinetics and dosage
regimen of cefpirome in febrile cross-bred calves Iran J Pharmacol Ther 10(1) 17-20
35 Abo-El- Sooud K and Tohamy MA (2011) Comparative pharmacokinetics and milk
concentrations of ceftazidime in healthy and mastitic goats Insight Pharmaceut Sci
1(1) 11-17
36 El-Hewaity M Abd El Latif A Soliman A and Aboubakr M (2014) Comparative
pharmacokinetics of cefquinome (Cobactan 25) following repeated intramuscular
administrations in sheep and goats J Vet Med Doi 949642 1-5
37 El-Sayed M G A El-Komy A A A El barawy A M and Ibrahim D M A (2015)
Pharmacokinetics and tissue residues of ceftiofur in normal and Escherichia coli infected
chickens J Phys Pharm Adv 5(3) 574-582
38 Datta B Mandal TK and Chakraborty A K (2003) Pharmacokinetics of cefotaxime
in goats with experimentally induced kidney damage Ind J pharmacol (35) 173-176
39 Guerrini HV English BP Filippich J L Schneider J and Bourne D W (1986)
The pharmacokinetics of cefotaxime in dog Vet Rec 119(4) 81-83
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
40 Atef M Ramadan A Afifi N A and Youssef S A (1990) pharmacokinetic profile
of cefotaxime in goat Res Vet Sci 49(1) 34-38
41 Satish K G Chaudhary RK Srivastiva AK and Garg BD (1990) Pharmacokintics
and dosage regemine of cephalexine in buffulo calves (Bubalis Bubalis following single
intravenous and intramusculer adminsteration Veterinary research commuincation 14
59-62
42 Goudah A (2008) Pharmacokinetic parameters of ceftriaxone after single intravenous
and intramuscular administration in camels (Camelus Dromedarius) Res Vet Sci Jun
84(3) 483-9
43 Sharma SK Srivastava AK and Deore DM (2006) Effect of Ecoli
lipopolysaccharides ndashinduced fever on disposition pattern of cefotaxime in buffalo calves
Veterinarski Arhiv 76(6) 537-545
44 Baggot JD (1977) Priniciple of pharmacokinetics In principle of drug disposition in
domestic animals The physiological Basis of veterinary Clinical Pharmacology 1st ed
WB Saunders Co Philadelphi PA 168-179
45 Karmaker UK Datta BK Patra PH Prashant M Suman S Sar TK Chakaborty
AK and mandal KT (2011) Disposition kinetics of ceftizoxime in healthy and mastitic
goats after intravenous adminsteration Pharmacologyonline 3 935-946
46 Ringger NC Pearson EG Gronwall R Kohlepp S J (1996) Pharmacokinetics of
ceftriaxone in healthy horses Equine Vet J Nov 28(6) 476-9
47 Prawez S Raina R Dimitrova D panka NK Ahanger AA Verma PK (2010) The
pharmacokinetics of cefipime in goats following single dose iv and im adminsteration
Turk j vet Anima Sci 34(5) 427-431
48 Baggot JD (1980) Distribution of antimicrobial agents in normal and diseased animals
JAVMA 19(76) 1085-1090
49 Haddad N S Pedersoli W M Ravis W R Fazeli M H and Carson Jr R L (1985)
Pharmacokinetics of gentamicin at steady-state in ponies serum urine and endometrial
concentrations Am J Vet Res 46(6) 1268-1271
50 Gupta JK Chaudhary RK and Dumka VK (2008) Pharmacokinetics after single
intramuscuker adminsrerarion and in-vitro binding plasma protein of cefoprazone in cross
bred calves Veterinaski Arhiv 78(5) 441-448
51 Al Taher AY (2010) Pharmacokinetics of cefquinome in camels J An Vet Ad 9(4)
848-852
wwwwjppscom Vol 5 Issue 01 2016
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
52 Rajput N Dumka V K and Sandhu HS (2012) Pharmacokinetics and in- vitro
plasma protein binding of cefpirome in cattle Veterinaski Arhiv 82(1) 1-9
53 RebueltoM Albarellos G Ambros L Kreil V Montoya L Bonafine R Otero P
Hallu R (2002) Pharmacokinetics of ceftriaxone administered by the intravenous
intramuscular or subcutaneous routes to dogs J Vet Pharmacol Ther Feb 25(1) 73-6
54 Patel RB Bhavsar SK Solanki PF Patel JH Varia RD Modi Falguni D and
Patel MD (2013) Pharmacokinetics of cefpirome following intravenous and
intramuscular administration in cow calves Sci Int 1(11) 371-374
55 Maradiya J J Goriya H V Bhavsar S K Patel U D and Thaker A M (2010)
Pharmacokinetics of ceftriaxone in calves Veterinarski arhiv 80(1) 1-9
56 Inges R MJ Fillastre J Godin M Leroy A and Humbert G (1982) The
Pharmacokinetics of cefotaxime and its metabolites in subjects with normal and impaired
renal function Clin Infect Dis (4) 379-391
57 Mcelroy D Ravis W R and Clark C H (1986) Pharmacokinetics of cefotaxime in
the domestic cats Am J Vet Res 47(1) 86-88
58 El-Sayed MG Atef M and El-Komy AA (1994) Disposition kinetic of cephradine in
normal and Escherichia coli infected goats Dtsch Tierarztl Wochenschr 101(2) 56-60
59 Soback S and Ziv G (1988) Pharmacokinetics and bioavailability of ceftriaxone
administered intravenously and intramuscularly to calves Am J Vet Res 49 535-538
60 Sharma S K and Srivastava A K (2003) Cefotaxime pharmacokinetics in male
buffalo calves following multiple dosing Veterinarski arhiv 73(4) 191-197
61 Abdulgafar O J Shaibu O B and Emmanuel U E (2011) Effect of Salmonella
typhymurium infection on the pharmacokinetics of ceftriaxone in sokoto red goats Niger
J Basic Applied Sci 19(1) 49-54
62 Ranjan R Birendra K R Amita R and Sanjeet K S (2011) Effect of Effect of E coli E
coli endotoxin induced fever on the pharmacokinetic profile and dosage regimen of
ceftriaxone in sheep (Ovis aries) Veterinarski arhiv 81(4) 423-432
63 Etuk EU and Onyeyili PA (2006) The effect of Salmonella infection on the plasma
kinetic of chloramphenicol in the sokoto red goats Inter J Pharmacol 2(1) 28-32
64 Wang E Bergeron Y and Bergeron MG (2005) Ceftriaxone pharmacokinetics in
interleukin-10-treated murine pneumococcal pneumonia J Antimicrob Chemother 55
721ndash726
wwwwjppscom Vol 5 Issue 01 2016
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Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
65 El-Sayed MG Hatem ME and El-Komy AA (1989) Disposition kinetic of
gentamicin in normal and endometric cow using microbiological assay Dtsch Tierarztl
Wochenschr 96(8) 412-415
66 Aramyona JJ Mora J Fraile LJ Garcia MA Abadia AR and Breganate MA
(1996) Penetration of enrofloxacin and ciprofloxacin into breast milk and
pharmacokinetics of the drugs in lacating rabbits and neonatal offspring Am J Vet Res
57(4) 547-553
67 Rusmussen F (1966) Studies on the mammary excretion and absorbtion of drugs Vet
Rec (87) 14-18
68 Alkinson A and Begg E (1990) Prediction of drug distribution into human milk from
physicochemical characteristics Clin Pharmacokinet 18(2) 151-167
69 Kenneth F (1997) Drug distribution in human milk Aust Prescr 20(2) 35-40
70 Aleksić M Savić V Popović G Burić N and Kapetanović V (2005) Acidity
constants of cefetamet cefotaxime and ceftriaxone the effect of the substituent at C3
position J Pharm Biomed Anal 39(3-4) 752-756
71 Prades M Brown M P Gronwall R and Miles N S (1988) Pharmacokinetics of
sodium cephapirin in lactating dairy cows Am J Vet Res 49(11) 1888-1890
72 Holazo A A Patel I H Weinfeld R E Konikoff J J and Parsonnet M (1986)
Ceftriaxone pharmacokinetics following multiple intramuscular dosing Euro J Clin
Pharmacol 30(1) 109-112
wwwwjppscom Vol 5 Issue 01 2016
1451
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
in comparison to normal sheepOn contrast[43]
reported that peak plasma level of cefotaxime
in febrile buffalo calves was higher than healthy buffalo calves
In this study the total body clearance (CLtot) in normal goats are significantly lower than in
Salmonella typhimurium infected goats This result supported by[61]
and[63]
fever and
inflammation are cardinal features in bacterial infection which may in turn caused an
increase in heart rate and cardiac output increasing blood flow to the liver and kidneys all
these could lead to increased in the rate at which the drug was delivered to both organs which
were important sites of drug excretion This might somewhat explain the increase in the total
body clearance in infected goats This result is differ than that reported by[64]
who observed
that the clearance of ceftriaxone was significantly reduced in infected mice than in non
infected animals
The highest concentrations of ceftriaxone in milk are recorded 4 hours after each
intramuscular injection with a significant lower value in Salmonella typhimurium infected
goats than in normal goats This might be attributed to accumulation of drug in the inflammed
tissues[48]
This result is similar to those reported by[6559]
who found that milk concentrations
of gentamicin and cephradine were significantly lower in infected goats and cattle than in
normal ones respectively
The mechanism of blood-milk passage of ceftriaxone could be explained on the basis of the
non-ionic passive diffusion principle[66]
reported that most drug cross-lipid membranes by
passive diffusion in the unbound nonndashionized state and the extent of diffusion is greatly
influenced by the physicochemical properties of the drug[6768]
Almost all drugs passed into milk from maternal plasma by passive diffusion the milkserum
ratio was affected by the composition of the milk (aqueous lipid protein and pH) and the
physicochemical characteristics of the drug (protein binding lipophilicity and pKa)[69]
Milk
contains substantially more lipid and less protein than serum and is slightly more acidic
Therefore drugs which tend to concentrated in milk are weak bases with low serum protein
binding and high lipid solubility Ceftriaxone have three ionization groups carboxylic amide
and aminothiazole also possesses an hydroxytriazinone group as new and additional
ionization center[70]
these compounds are sufficiently lipid- soluble to be able to penetrate
tissues
wwwwjppscom Vol 5 Issue 01 2016
1452
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
The dose of ceftriaxone used in the present study induced therapeutically concentrations in
milk These concentrations suggested that ceftriaxone would be efficacious in treatment of
mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily
for 3-5 days
The study showed that the urine concentrations of ceftriaxone are greater than the concurrent
serum concentrations following intramuscular injection This observation is similar to those
reported in cows after cephapirin administrations[71]
In the present study urine concentrations of ceftriaxone increased with the repetition of
dosing This observation supported by[72]
after repeated intramuscular administrations of
ceftriaxone in healthy volunteeres
The mean peak urine concentrations of ceftriaxone were reached 2 hours after each
intramuscular injection The lower urine ceftriaxone concentrations in Salmonella
typhimurium infected goats than in normal goats might be attributed to the accumulation of
the drug in the inflamed tissues[48]
The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower
ratio in Salmonella typhimurium infected goats than in normal goats at different time of
sampling This indicates that glomerular filteration seemed to be the main pathway of
ceftriaxone elimination This observation supported by[59]
who found that the ratio between
cephradine clearance from blood of goats to creatinine clearance showed a marked decrease
in Escherichia-coli infected goats than in normal goats This indicated that glomerular
filteration seemed to be the main pathway of cephradine elimination with a limited rate of
tubular reabsorption
CONCLUSION
The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value
referred a better absorption of ceftriaxone from its site of intramuscular administration The
high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular
administrations suggested that ceftriaxone could be used for treatment of mastitis caused by
Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats
The high concentrations of ceftriaxone in urine after repeated intramuscular administrations
suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections
wwwwjppscom Vol 5 Issue 01 2016
1453
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in
goats
REFERANCES
1 Neu HC Merpol NJ and Fukp (1981) Antibacterial activity of ceftriaxone
abetalactamase stable cephalosporines Antimicrobial agents and chemotherapy 19
414-423
2 Richard DM Heel RC Brogden RN Speight TM Avery GS (1984) Ceftriaxone a
review of its antibacterial activity pharmacological properties and therapeutic uses
Drugs 27 469-527
3 Brogden RN and Ward A (1988) Ceftriaxone a reappraisal of its antibacterial activity
and pharmacokinetic properties and an update on its therapeutic use with particular
reference to once-daily administration Drugs 35 604-645
4 Waxman DJ and Strominger JL (1983) Penicillin-binding proteins and the
mechanism of action of beta-lactam antibiotics Annu Rev Biochem 52(1) 825-869
5 Christ W (1991) properties of cephalosporines Infestion 19 244-252
6 Goonetilleke AK Dev D Aziz I Hughes C Smith MJ Basran GS (1996) A
comparative analysis of pharmacokinetics of ceftriaxone in serum and pleural fluid in
humans a study of once daily administration by intramuscular intravenous routes J
Antimicrob Chemother Dec 38(6) 969-76
7 Guerrini VH Filippich LJ Cao G R English PB Bourne DW (1985)
Pharmacokinetics of cefaronide ceftriaxone and cefperazone in sheep J Vet Pharmacol
Ther 8(2) 120-7
8 Swati Tiwari S Patel UD Bhavsar SK and Thaker AM (2010) Pharmacokinetics
and Bioavailability of Ceftriaxone in Patanwadi Sheep Online veterinary journal 5(2)
9 Ismail MM (2005) Pharmacokinetics urinary and mammary excretion of ceftriaxone in
lactating goats J Vet Med A Physiol Pathol Clin Med Sep 52(7) 354-8
10 Rajinder R prawez S Srivastiva AS (2005) Pharmacokinetics and dosage regimen of
ceftriaxone following its single ntramuscular adminsteration in kagani breed of goats
(Capra Hircus) Journal of reaserch 4(2) 91-93
11 Tiwari S Swati Bhavsar SK Patel UD and Thaker AM (2009) Disposition of
Ceftriaxone in Goats (Capra hircus) Online veterinary journal 4(2)
12 Dardi MS Sharma SK and Srivastava AK (2004) Pharmacokinetics and Dosage
regimen of ceftriaxone in buffalo calves Vet Res Commun 28 331-338
wwwwjppscom Vol 5 Issue 01 2016
1454
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
13 Gohil P V Patel U D Bhavsar S K Thaker A M (2009) Pharmacokinetics of
ceftriaxone in buffalo calves (Bubalus bubalis) following intravenous and intramuscular
administration Iranian Journal of Veterinary Research 10(1) 33-37
14 Maradyia JJ Harshad VG Shaliesh KB Urvesh DP Aswin MT (2010)
Pharmacokinetics of ceftriaxone in calves Veterinarski arhiv 80(1) 1-9 2010
15 Albarellos GA Kreil VE Landoni MF (2007) Pharmacokinetics of ceftriaxone after
intravenous intramuscular and subcutaneous administration to domestic cats J Vet
Pharmacol Ther Aug 30(4) 345-52
16 Johal B and Srivastava AK (1998) Pharmacokinetics urinary excretion and dosage
regimen of ceftriaxone in Crossbred cow calves 68(10)
17 Otesile EB Ahmed G and Adetosoye AI (1990) Experimental infection of Red Sokoto
goats with Salmonella typhimurium Rev Eacutelev Meacuted Veacutet Pays trop 43(1) 49-53
18 Iroha I R Amadi E S Orji JO and Esimone C O (2008) In vitro evaluation of the
activity of colloidal silver concentrate against Pseudomonas aeruginosa isolated from
postoperative wound infection Scientific Research and Essay May 3(5) 209-211
19 Bennett JV Brodie JL Benner E and Kibry W (1966) Simplified accurate method
for antibiotic assay for clinical specimen Appl Microbial 14 170-175
20 Grove DC and Randall WA (1955) Assay methods of antibiotics Medical
encyclopedia New York 79(12) 259-32
21 Murray R (1984) Creatinin kaplane et al Clinc Chem Ther CV Mosby Co S Louis
Toronto Princeton 1261-1266 and 418
22 Baggot JD (1978a) Some aspect of clinical pharmacokinetics in veterinary medicine I J
Vet Pharm Ther 1 5-18
23 Baggot JD (1978b) Some aspect of clinical pharmacokinetics in veterinary medicine II
J Vet Pharm Ther 1 111-118
24 Snedecor GW and Cokran WG (1980) Statistical method 7th
Ed The Iowa state
university press Ames Iowa USA 39-63
25 Goudah A Shin HC Shim JH Abd El-Aty AM (2006) Characterization of the
relationship between serum and milk residu disposition of ceftriaxone in lactating ewe J
Vet Pharmacol Ther Aug 29(4) 307-12
26 Jayesh J M Harshad V G Shailesh K B Urvesh D P and Aswin M T (2010)
Pharmacokinetics of ceftriaxone in calves Veterinarski arshiv 80(1) 1-9
wwwwjppscom Vol 5 Issue 01 2016
1455
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
27 Abd-El-Aty AM Goudah A and Abo E S K (2001) Pharmacokinetics
intramuscular bioavailability and tissue residue profiles of ceftazidime in a rabbit
model Dtsch Tierarztl Wochenschr 108(4) 168-171
28 Gardner S Y and Papich M G (2001) Comparison of cefepime pharmacokinetics in
neonatal foals and adult dogs J Vet Pharmacol Therap 24(3) 187-192
29 Ismail M (2005a) Pharmacokinetics of cefepime administered by iv and im routes to
ewes J Vet Pharmacol Therap 28(6) 499-503
30 Patel U D Bhavsar S K and Thaker A M (2006) Pharmacokinetics and dosage
regimen of cefepime following single dose intravenous administration in calves Iran J
Pharmacol Therapeut 5(2) 127-130
31 El-Gendy AAM Tohamy MA and Ismail M (2007) Comparative pharmacokinetic
and renal clearance study of ceftiofur in cross breed friesian and buffalo calves BS Vet
Med J 17(1) 69-77
32 Joshi B and Kumar Sharma S (2009) The pharmacokinetics of cefepime in E coli
lipopolysaccharide induced febrile buffalo calves Veterinarski arhiv 79(6) 523-530
33 Tohamy MA (2008) Pharmacokinetics of ceftiofur sodium administered concomitantly
with dipyrone in healthy and feverish cows J Egypt Soc Pharmacol Exp Ther 29(2)
10-15
34 Rajput N Kumar V D and Sandhu HS (2011) Pharmacokinetics and dosage
regimen of cefpirome in febrile cross-bred calves Iran J Pharmacol Ther 10(1) 17-20
35 Abo-El- Sooud K and Tohamy MA (2011) Comparative pharmacokinetics and milk
concentrations of ceftazidime in healthy and mastitic goats Insight Pharmaceut Sci
1(1) 11-17
36 El-Hewaity M Abd El Latif A Soliman A and Aboubakr M (2014) Comparative
pharmacokinetics of cefquinome (Cobactan 25) following repeated intramuscular
administrations in sheep and goats J Vet Med Doi 949642 1-5
37 El-Sayed M G A El-Komy A A A El barawy A M and Ibrahim D M A (2015)
Pharmacokinetics and tissue residues of ceftiofur in normal and Escherichia coli infected
chickens J Phys Pharm Adv 5(3) 574-582
38 Datta B Mandal TK and Chakraborty A K (2003) Pharmacokinetics of cefotaxime
in goats with experimentally induced kidney damage Ind J pharmacol (35) 173-176
39 Guerrini HV English BP Filippich J L Schneider J and Bourne D W (1986)
The pharmacokinetics of cefotaxime in dog Vet Rec 119(4) 81-83
wwwwjppscom Vol 5 Issue 01 2016
1456
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
40 Atef M Ramadan A Afifi N A and Youssef S A (1990) pharmacokinetic profile
of cefotaxime in goat Res Vet Sci 49(1) 34-38
41 Satish K G Chaudhary RK Srivastiva AK and Garg BD (1990) Pharmacokintics
and dosage regemine of cephalexine in buffulo calves (Bubalis Bubalis following single
intravenous and intramusculer adminsteration Veterinary research commuincation 14
59-62
42 Goudah A (2008) Pharmacokinetic parameters of ceftriaxone after single intravenous
and intramuscular administration in camels (Camelus Dromedarius) Res Vet Sci Jun
84(3) 483-9
43 Sharma SK Srivastava AK and Deore DM (2006) Effect of Ecoli
lipopolysaccharides ndashinduced fever on disposition pattern of cefotaxime in buffalo calves
Veterinarski Arhiv 76(6) 537-545
44 Baggot JD (1977) Priniciple of pharmacokinetics In principle of drug disposition in
domestic animals The physiological Basis of veterinary Clinical Pharmacology 1st ed
WB Saunders Co Philadelphi PA 168-179
45 Karmaker UK Datta BK Patra PH Prashant M Suman S Sar TK Chakaborty
AK and mandal KT (2011) Disposition kinetics of ceftizoxime in healthy and mastitic
goats after intravenous adminsteration Pharmacologyonline 3 935-946
46 Ringger NC Pearson EG Gronwall R Kohlepp S J (1996) Pharmacokinetics of
ceftriaxone in healthy horses Equine Vet J Nov 28(6) 476-9
47 Prawez S Raina R Dimitrova D panka NK Ahanger AA Verma PK (2010) The
pharmacokinetics of cefipime in goats following single dose iv and im adminsteration
Turk j vet Anima Sci 34(5) 427-431
48 Baggot JD (1980) Distribution of antimicrobial agents in normal and diseased animals
JAVMA 19(76) 1085-1090
49 Haddad N S Pedersoli W M Ravis W R Fazeli M H and Carson Jr R L (1985)
Pharmacokinetics of gentamicin at steady-state in ponies serum urine and endometrial
concentrations Am J Vet Res 46(6) 1268-1271
50 Gupta JK Chaudhary RK and Dumka VK (2008) Pharmacokinetics after single
intramuscuker adminsrerarion and in-vitro binding plasma protein of cefoprazone in cross
bred calves Veterinaski Arhiv 78(5) 441-448
51 Al Taher AY (2010) Pharmacokinetics of cefquinome in camels J An Vet Ad 9(4)
848-852
wwwwjppscom Vol 5 Issue 01 2016
1457
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
52 Rajput N Dumka V K and Sandhu HS (2012) Pharmacokinetics and in- vitro
plasma protein binding of cefpirome in cattle Veterinaski Arhiv 82(1) 1-9
53 RebueltoM Albarellos G Ambros L Kreil V Montoya L Bonafine R Otero P
Hallu R (2002) Pharmacokinetics of ceftriaxone administered by the intravenous
intramuscular or subcutaneous routes to dogs J Vet Pharmacol Ther Feb 25(1) 73-6
54 Patel RB Bhavsar SK Solanki PF Patel JH Varia RD Modi Falguni D and
Patel MD (2013) Pharmacokinetics of cefpirome following intravenous and
intramuscular administration in cow calves Sci Int 1(11) 371-374
55 Maradiya J J Goriya H V Bhavsar S K Patel U D and Thaker A M (2010)
Pharmacokinetics of ceftriaxone in calves Veterinarski arhiv 80(1) 1-9
56 Inges R MJ Fillastre J Godin M Leroy A and Humbert G (1982) The
Pharmacokinetics of cefotaxime and its metabolites in subjects with normal and impaired
renal function Clin Infect Dis (4) 379-391
57 Mcelroy D Ravis W R and Clark C H (1986) Pharmacokinetics of cefotaxime in
the domestic cats Am J Vet Res 47(1) 86-88
58 El-Sayed MG Atef M and El-Komy AA (1994) Disposition kinetic of cephradine in
normal and Escherichia coli infected goats Dtsch Tierarztl Wochenschr 101(2) 56-60
59 Soback S and Ziv G (1988) Pharmacokinetics and bioavailability of ceftriaxone
administered intravenously and intramuscularly to calves Am J Vet Res 49 535-538
60 Sharma S K and Srivastava A K (2003) Cefotaxime pharmacokinetics in male
buffalo calves following multiple dosing Veterinarski arhiv 73(4) 191-197
61 Abdulgafar O J Shaibu O B and Emmanuel U E (2011) Effect of Salmonella
typhymurium infection on the pharmacokinetics of ceftriaxone in sokoto red goats Niger
J Basic Applied Sci 19(1) 49-54
62 Ranjan R Birendra K R Amita R and Sanjeet K S (2011) Effect of Effect of E coli E
coli endotoxin induced fever on the pharmacokinetic profile and dosage regimen of
ceftriaxone in sheep (Ovis aries) Veterinarski arhiv 81(4) 423-432
63 Etuk EU and Onyeyili PA (2006) The effect of Salmonella infection on the plasma
kinetic of chloramphenicol in the sokoto red goats Inter J Pharmacol 2(1) 28-32
64 Wang E Bergeron Y and Bergeron MG (2005) Ceftriaxone pharmacokinetics in
interleukin-10-treated murine pneumococcal pneumonia J Antimicrob Chemother 55
721ndash726
wwwwjppscom Vol 5 Issue 01 2016
1458
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
65 El-Sayed MG Hatem ME and El-Komy AA (1989) Disposition kinetic of
gentamicin in normal and endometric cow using microbiological assay Dtsch Tierarztl
Wochenschr 96(8) 412-415
66 Aramyona JJ Mora J Fraile LJ Garcia MA Abadia AR and Breganate MA
(1996) Penetration of enrofloxacin and ciprofloxacin into breast milk and
pharmacokinetics of the drugs in lacating rabbits and neonatal offspring Am J Vet Res
57(4) 547-553
67 Rusmussen F (1966) Studies on the mammary excretion and absorbtion of drugs Vet
Rec (87) 14-18
68 Alkinson A and Begg E (1990) Prediction of drug distribution into human milk from
physicochemical characteristics Clin Pharmacokinet 18(2) 151-167
69 Kenneth F (1997) Drug distribution in human milk Aust Prescr 20(2) 35-40
70 Aleksić M Savić V Popović G Burić N and Kapetanović V (2005) Acidity
constants of cefetamet cefotaxime and ceftriaxone the effect of the substituent at C3
position J Pharm Biomed Anal 39(3-4) 752-756
71 Prades M Brown M P Gronwall R and Miles N S (1988) Pharmacokinetics of
sodium cephapirin in lactating dairy cows Am J Vet Res 49(11) 1888-1890
72 Holazo A A Patel I H Weinfeld R E Konikoff J J and Parsonnet M (1986)
Ceftriaxone pharmacokinetics following multiple intramuscular dosing Euro J Clin
Pharmacol 30(1) 109-112
wwwwjppscom Vol 5 Issue 01 2016
1452
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
The dose of ceftriaxone used in the present study induced therapeutically concentrations in
milk These concentrations suggested that ceftriaxone would be efficacious in treatment of
mastitis caused by sensitive organisms in lactating goats at dose 20 mgkg bwt Twice daily
for 3-5 days
The study showed that the urine concentrations of ceftriaxone are greater than the concurrent
serum concentrations following intramuscular injection This observation is similar to those
reported in cows after cephapirin administrations[71]
In the present study urine concentrations of ceftriaxone increased with the repetition of
dosing This observation supported by[72]
after repeated intramuscular administrations of
ceftriaxone in healthy volunteeres
The mean peak urine concentrations of ceftriaxone were reached 2 hours after each
intramuscular injection The lower urine ceftriaxone concentrations in Salmonella
typhimurium infected goats than in normal goats might be attributed to the accumulation of
the drug in the inflamed tissues[48]
The ratio between ceftriaxone clearance and creatinine clearance revealed a significant lower
ratio in Salmonella typhimurium infected goats than in normal goats at different time of
sampling This indicates that glomerular filteration seemed to be the main pathway of
ceftriaxone elimination This observation supported by[59]
who found that the ratio between
cephradine clearance from blood of goats to creatinine clearance showed a marked decrease
in Escherichia-coli infected goats than in normal goats This indicated that glomerular
filteration seemed to be the main pathway of cephradine elimination with a limited rate of
tubular reabsorption
CONCLUSION
The intramuscular bioavailability of ceftriaxone in normal goats was 6128 This value
referred a better absorption of ceftriaxone from its site of intramuscular administration The
high milk concentrations of ceftriaxone in lactating goats after repeated intramuscular
administrations suggested that ceftriaxone could be used for treatment of mastitis caused by
Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in lactating goats
The high concentrations of ceftriaxone in urine after repeated intramuscular administrations
suggested that ceftriaxone is a suitable antimicrobial for treatment of urinary tract infections
wwwwjppscom Vol 5 Issue 01 2016
1453
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in
goats
REFERANCES
1 Neu HC Merpol NJ and Fukp (1981) Antibacterial activity of ceftriaxone
abetalactamase stable cephalosporines Antimicrobial agents and chemotherapy 19
414-423
2 Richard DM Heel RC Brogden RN Speight TM Avery GS (1984) Ceftriaxone a
review of its antibacterial activity pharmacological properties and therapeutic uses
Drugs 27 469-527
3 Brogden RN and Ward A (1988) Ceftriaxone a reappraisal of its antibacterial activity
and pharmacokinetic properties and an update on its therapeutic use with particular
reference to once-daily administration Drugs 35 604-645
4 Waxman DJ and Strominger JL (1983) Penicillin-binding proteins and the
mechanism of action of beta-lactam antibiotics Annu Rev Biochem 52(1) 825-869
5 Christ W (1991) properties of cephalosporines Infestion 19 244-252
6 Goonetilleke AK Dev D Aziz I Hughes C Smith MJ Basran GS (1996) A
comparative analysis of pharmacokinetics of ceftriaxone in serum and pleural fluid in
humans a study of once daily administration by intramuscular intravenous routes J
Antimicrob Chemother Dec 38(6) 969-76
7 Guerrini VH Filippich LJ Cao G R English PB Bourne DW (1985)
Pharmacokinetics of cefaronide ceftriaxone and cefperazone in sheep J Vet Pharmacol
Ther 8(2) 120-7
8 Swati Tiwari S Patel UD Bhavsar SK and Thaker AM (2010) Pharmacokinetics
and Bioavailability of Ceftriaxone in Patanwadi Sheep Online veterinary journal 5(2)
9 Ismail MM (2005) Pharmacokinetics urinary and mammary excretion of ceftriaxone in
lactating goats J Vet Med A Physiol Pathol Clin Med Sep 52(7) 354-8
10 Rajinder R prawez S Srivastiva AS (2005) Pharmacokinetics and dosage regimen of
ceftriaxone following its single ntramuscular adminsteration in kagani breed of goats
(Capra Hircus) Journal of reaserch 4(2) 91-93
11 Tiwari S Swati Bhavsar SK Patel UD and Thaker AM (2009) Disposition of
Ceftriaxone in Goats (Capra hircus) Online veterinary journal 4(2)
12 Dardi MS Sharma SK and Srivastava AK (2004) Pharmacokinetics and Dosage
regimen of ceftriaxone in buffalo calves Vet Res Commun 28 331-338
wwwwjppscom Vol 5 Issue 01 2016
1454
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
13 Gohil P V Patel U D Bhavsar S K Thaker A M (2009) Pharmacokinetics of
ceftriaxone in buffalo calves (Bubalus bubalis) following intravenous and intramuscular
administration Iranian Journal of Veterinary Research 10(1) 33-37
14 Maradyia JJ Harshad VG Shaliesh KB Urvesh DP Aswin MT (2010)
Pharmacokinetics of ceftriaxone in calves Veterinarski arhiv 80(1) 1-9 2010
15 Albarellos GA Kreil VE Landoni MF (2007) Pharmacokinetics of ceftriaxone after
intravenous intramuscular and subcutaneous administration to domestic cats J Vet
Pharmacol Ther Aug 30(4) 345-52
16 Johal B and Srivastava AK (1998) Pharmacokinetics urinary excretion and dosage
regimen of ceftriaxone in Crossbred cow calves 68(10)
17 Otesile EB Ahmed G and Adetosoye AI (1990) Experimental infection of Red Sokoto
goats with Salmonella typhimurium Rev Eacutelev Meacuted Veacutet Pays trop 43(1) 49-53
18 Iroha I R Amadi E S Orji JO and Esimone C O (2008) In vitro evaluation of the
activity of colloidal silver concentrate against Pseudomonas aeruginosa isolated from
postoperative wound infection Scientific Research and Essay May 3(5) 209-211
19 Bennett JV Brodie JL Benner E and Kibry W (1966) Simplified accurate method
for antibiotic assay for clinical specimen Appl Microbial 14 170-175
20 Grove DC and Randall WA (1955) Assay methods of antibiotics Medical
encyclopedia New York 79(12) 259-32
21 Murray R (1984) Creatinin kaplane et al Clinc Chem Ther CV Mosby Co S Louis
Toronto Princeton 1261-1266 and 418
22 Baggot JD (1978a) Some aspect of clinical pharmacokinetics in veterinary medicine I J
Vet Pharm Ther 1 5-18
23 Baggot JD (1978b) Some aspect of clinical pharmacokinetics in veterinary medicine II
J Vet Pharm Ther 1 111-118
24 Snedecor GW and Cokran WG (1980) Statistical method 7th
Ed The Iowa state
university press Ames Iowa USA 39-63
25 Goudah A Shin HC Shim JH Abd El-Aty AM (2006) Characterization of the
relationship between serum and milk residu disposition of ceftriaxone in lactating ewe J
Vet Pharmacol Ther Aug 29(4) 307-12
26 Jayesh J M Harshad V G Shailesh K B Urvesh D P and Aswin M T (2010)
Pharmacokinetics of ceftriaxone in calves Veterinarski arshiv 80(1) 1-9
wwwwjppscom Vol 5 Issue 01 2016
1455
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
27 Abd-El-Aty AM Goudah A and Abo E S K (2001) Pharmacokinetics
intramuscular bioavailability and tissue residue profiles of ceftazidime in a rabbit
model Dtsch Tierarztl Wochenschr 108(4) 168-171
28 Gardner S Y and Papich M G (2001) Comparison of cefepime pharmacokinetics in
neonatal foals and adult dogs J Vet Pharmacol Therap 24(3) 187-192
29 Ismail M (2005a) Pharmacokinetics of cefepime administered by iv and im routes to
ewes J Vet Pharmacol Therap 28(6) 499-503
30 Patel U D Bhavsar S K and Thaker A M (2006) Pharmacokinetics and dosage
regimen of cefepime following single dose intravenous administration in calves Iran J
Pharmacol Therapeut 5(2) 127-130
31 El-Gendy AAM Tohamy MA and Ismail M (2007) Comparative pharmacokinetic
and renal clearance study of ceftiofur in cross breed friesian and buffalo calves BS Vet
Med J 17(1) 69-77
32 Joshi B and Kumar Sharma S (2009) The pharmacokinetics of cefepime in E coli
lipopolysaccharide induced febrile buffalo calves Veterinarski arhiv 79(6) 523-530
33 Tohamy MA (2008) Pharmacokinetics of ceftiofur sodium administered concomitantly
with dipyrone in healthy and feverish cows J Egypt Soc Pharmacol Exp Ther 29(2)
10-15
34 Rajput N Kumar V D and Sandhu HS (2011) Pharmacokinetics and dosage
regimen of cefpirome in febrile cross-bred calves Iran J Pharmacol Ther 10(1) 17-20
35 Abo-El- Sooud K and Tohamy MA (2011) Comparative pharmacokinetics and milk
concentrations of ceftazidime in healthy and mastitic goats Insight Pharmaceut Sci
1(1) 11-17
36 El-Hewaity M Abd El Latif A Soliman A and Aboubakr M (2014) Comparative
pharmacokinetics of cefquinome (Cobactan 25) following repeated intramuscular
administrations in sheep and goats J Vet Med Doi 949642 1-5
37 El-Sayed M G A El-Komy A A A El barawy A M and Ibrahim D M A (2015)
Pharmacokinetics and tissue residues of ceftiofur in normal and Escherichia coli infected
chickens J Phys Pharm Adv 5(3) 574-582
38 Datta B Mandal TK and Chakraborty A K (2003) Pharmacokinetics of cefotaxime
in goats with experimentally induced kidney damage Ind J pharmacol (35) 173-176
39 Guerrini HV English BP Filippich J L Schneider J and Bourne D W (1986)
The pharmacokinetics of cefotaxime in dog Vet Rec 119(4) 81-83
wwwwjppscom Vol 5 Issue 01 2016
1456
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
40 Atef M Ramadan A Afifi N A and Youssef S A (1990) pharmacokinetic profile
of cefotaxime in goat Res Vet Sci 49(1) 34-38
41 Satish K G Chaudhary RK Srivastiva AK and Garg BD (1990) Pharmacokintics
and dosage regemine of cephalexine in buffulo calves (Bubalis Bubalis following single
intravenous and intramusculer adminsteration Veterinary research commuincation 14
59-62
42 Goudah A (2008) Pharmacokinetic parameters of ceftriaxone after single intravenous
and intramuscular administration in camels (Camelus Dromedarius) Res Vet Sci Jun
84(3) 483-9
43 Sharma SK Srivastava AK and Deore DM (2006) Effect of Ecoli
lipopolysaccharides ndashinduced fever on disposition pattern of cefotaxime in buffalo calves
Veterinarski Arhiv 76(6) 537-545
44 Baggot JD (1977) Priniciple of pharmacokinetics In principle of drug disposition in
domestic animals The physiological Basis of veterinary Clinical Pharmacology 1st ed
WB Saunders Co Philadelphi PA 168-179
45 Karmaker UK Datta BK Patra PH Prashant M Suman S Sar TK Chakaborty
AK and mandal KT (2011) Disposition kinetics of ceftizoxime in healthy and mastitic
goats after intravenous adminsteration Pharmacologyonline 3 935-946
46 Ringger NC Pearson EG Gronwall R Kohlepp S J (1996) Pharmacokinetics of
ceftriaxone in healthy horses Equine Vet J Nov 28(6) 476-9
47 Prawez S Raina R Dimitrova D panka NK Ahanger AA Verma PK (2010) The
pharmacokinetics of cefipime in goats following single dose iv and im adminsteration
Turk j vet Anima Sci 34(5) 427-431
48 Baggot JD (1980) Distribution of antimicrobial agents in normal and diseased animals
JAVMA 19(76) 1085-1090
49 Haddad N S Pedersoli W M Ravis W R Fazeli M H and Carson Jr R L (1985)
Pharmacokinetics of gentamicin at steady-state in ponies serum urine and endometrial
concentrations Am J Vet Res 46(6) 1268-1271
50 Gupta JK Chaudhary RK and Dumka VK (2008) Pharmacokinetics after single
intramuscuker adminsrerarion and in-vitro binding plasma protein of cefoprazone in cross
bred calves Veterinaski Arhiv 78(5) 441-448
51 Al Taher AY (2010) Pharmacokinetics of cefquinome in camels J An Vet Ad 9(4)
848-852
wwwwjppscom Vol 5 Issue 01 2016
1457
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
52 Rajput N Dumka V K and Sandhu HS (2012) Pharmacokinetics and in- vitro
plasma protein binding of cefpirome in cattle Veterinaski Arhiv 82(1) 1-9
53 RebueltoM Albarellos G Ambros L Kreil V Montoya L Bonafine R Otero P
Hallu R (2002) Pharmacokinetics of ceftriaxone administered by the intravenous
intramuscular or subcutaneous routes to dogs J Vet Pharmacol Ther Feb 25(1) 73-6
54 Patel RB Bhavsar SK Solanki PF Patel JH Varia RD Modi Falguni D and
Patel MD (2013) Pharmacokinetics of cefpirome following intravenous and
intramuscular administration in cow calves Sci Int 1(11) 371-374
55 Maradiya J J Goriya H V Bhavsar S K Patel U D and Thaker A M (2010)
Pharmacokinetics of ceftriaxone in calves Veterinarski arhiv 80(1) 1-9
56 Inges R MJ Fillastre J Godin M Leroy A and Humbert G (1982) The
Pharmacokinetics of cefotaxime and its metabolites in subjects with normal and impaired
renal function Clin Infect Dis (4) 379-391
57 Mcelroy D Ravis W R and Clark C H (1986) Pharmacokinetics of cefotaxime in
the domestic cats Am J Vet Res 47(1) 86-88
58 El-Sayed MG Atef M and El-Komy AA (1994) Disposition kinetic of cephradine in
normal and Escherichia coli infected goats Dtsch Tierarztl Wochenschr 101(2) 56-60
59 Soback S and Ziv G (1988) Pharmacokinetics and bioavailability of ceftriaxone
administered intravenously and intramuscularly to calves Am J Vet Res 49 535-538
60 Sharma S K and Srivastava A K (2003) Cefotaxime pharmacokinetics in male
buffalo calves following multiple dosing Veterinarski arhiv 73(4) 191-197
61 Abdulgafar O J Shaibu O B and Emmanuel U E (2011) Effect of Salmonella
typhymurium infection on the pharmacokinetics of ceftriaxone in sokoto red goats Niger
J Basic Applied Sci 19(1) 49-54
62 Ranjan R Birendra K R Amita R and Sanjeet K S (2011) Effect of Effect of E coli E
coli endotoxin induced fever on the pharmacokinetic profile and dosage regimen of
ceftriaxone in sheep (Ovis aries) Veterinarski arhiv 81(4) 423-432
63 Etuk EU and Onyeyili PA (2006) The effect of Salmonella infection on the plasma
kinetic of chloramphenicol in the sokoto red goats Inter J Pharmacol 2(1) 28-32
64 Wang E Bergeron Y and Bergeron MG (2005) Ceftriaxone pharmacokinetics in
interleukin-10-treated murine pneumococcal pneumonia J Antimicrob Chemother 55
721ndash726
wwwwjppscom Vol 5 Issue 01 2016
1458
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
65 El-Sayed MG Hatem ME and El-Komy AA (1989) Disposition kinetic of
gentamicin in normal and endometric cow using microbiological assay Dtsch Tierarztl
Wochenschr 96(8) 412-415
66 Aramyona JJ Mora J Fraile LJ Garcia MA Abadia AR and Breganate MA
(1996) Penetration of enrofloxacin and ciprofloxacin into breast milk and
pharmacokinetics of the drugs in lacating rabbits and neonatal offspring Am J Vet Res
57(4) 547-553
67 Rusmussen F (1966) Studies on the mammary excretion and absorbtion of drugs Vet
Rec (87) 14-18
68 Alkinson A and Begg E (1990) Prediction of drug distribution into human milk from
physicochemical characteristics Clin Pharmacokinet 18(2) 151-167
69 Kenneth F (1997) Drug distribution in human milk Aust Prescr 20(2) 35-40
70 Aleksić M Savić V Popović G Burić N and Kapetanović V (2005) Acidity
constants of cefetamet cefotaxime and ceftriaxone the effect of the substituent at C3
position J Pharm Biomed Anal 39(3-4) 752-756
71 Prades M Brown M P Gronwall R and Miles N S (1988) Pharmacokinetics of
sodium cephapirin in lactating dairy cows Am J Vet Res 49(11) 1888-1890
72 Holazo A A Patel I H Weinfeld R E Konikoff J J and Parsonnet M (1986)
Ceftriaxone pharmacokinetics following multiple intramuscular dosing Euro J Clin
Pharmacol 30(1) 109-112
wwwwjppscom Vol 5 Issue 01 2016
1453
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
caused by Salmonella typhimurium and other sensitive microorganisms to ceftriaxone in
goats
REFERANCES
1 Neu HC Merpol NJ and Fukp (1981) Antibacterial activity of ceftriaxone
abetalactamase stable cephalosporines Antimicrobial agents and chemotherapy 19
414-423
2 Richard DM Heel RC Brogden RN Speight TM Avery GS (1984) Ceftriaxone a
review of its antibacterial activity pharmacological properties and therapeutic uses
Drugs 27 469-527
3 Brogden RN and Ward A (1988) Ceftriaxone a reappraisal of its antibacterial activity
and pharmacokinetic properties and an update on its therapeutic use with particular
reference to once-daily administration Drugs 35 604-645
4 Waxman DJ and Strominger JL (1983) Penicillin-binding proteins and the
mechanism of action of beta-lactam antibiotics Annu Rev Biochem 52(1) 825-869
5 Christ W (1991) properties of cephalosporines Infestion 19 244-252
6 Goonetilleke AK Dev D Aziz I Hughes C Smith MJ Basran GS (1996) A
comparative analysis of pharmacokinetics of ceftriaxone in serum and pleural fluid in
humans a study of once daily administration by intramuscular intravenous routes J
Antimicrob Chemother Dec 38(6) 969-76
7 Guerrini VH Filippich LJ Cao G R English PB Bourne DW (1985)
Pharmacokinetics of cefaronide ceftriaxone and cefperazone in sheep J Vet Pharmacol
Ther 8(2) 120-7
8 Swati Tiwari S Patel UD Bhavsar SK and Thaker AM (2010) Pharmacokinetics
and Bioavailability of Ceftriaxone in Patanwadi Sheep Online veterinary journal 5(2)
9 Ismail MM (2005) Pharmacokinetics urinary and mammary excretion of ceftriaxone in
lactating goats J Vet Med A Physiol Pathol Clin Med Sep 52(7) 354-8
10 Rajinder R prawez S Srivastiva AS (2005) Pharmacokinetics and dosage regimen of
ceftriaxone following its single ntramuscular adminsteration in kagani breed of goats
(Capra Hircus) Journal of reaserch 4(2) 91-93
11 Tiwari S Swati Bhavsar SK Patel UD and Thaker AM (2009) Disposition of
Ceftriaxone in Goats (Capra hircus) Online veterinary journal 4(2)
12 Dardi MS Sharma SK and Srivastava AK (2004) Pharmacokinetics and Dosage
regimen of ceftriaxone in buffalo calves Vet Res Commun 28 331-338
wwwwjppscom Vol 5 Issue 01 2016
1454
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
13 Gohil P V Patel U D Bhavsar S K Thaker A M (2009) Pharmacokinetics of
ceftriaxone in buffalo calves (Bubalus bubalis) following intravenous and intramuscular
administration Iranian Journal of Veterinary Research 10(1) 33-37
14 Maradyia JJ Harshad VG Shaliesh KB Urvesh DP Aswin MT (2010)
Pharmacokinetics of ceftriaxone in calves Veterinarski arhiv 80(1) 1-9 2010
15 Albarellos GA Kreil VE Landoni MF (2007) Pharmacokinetics of ceftriaxone after
intravenous intramuscular and subcutaneous administration to domestic cats J Vet
Pharmacol Ther Aug 30(4) 345-52
16 Johal B and Srivastava AK (1998) Pharmacokinetics urinary excretion and dosage
regimen of ceftriaxone in Crossbred cow calves 68(10)
17 Otesile EB Ahmed G and Adetosoye AI (1990) Experimental infection of Red Sokoto
goats with Salmonella typhimurium Rev Eacutelev Meacuted Veacutet Pays trop 43(1) 49-53
18 Iroha I R Amadi E S Orji JO and Esimone C O (2008) In vitro evaluation of the
activity of colloidal silver concentrate against Pseudomonas aeruginosa isolated from
postoperative wound infection Scientific Research and Essay May 3(5) 209-211
19 Bennett JV Brodie JL Benner E and Kibry W (1966) Simplified accurate method
for antibiotic assay for clinical specimen Appl Microbial 14 170-175
20 Grove DC and Randall WA (1955) Assay methods of antibiotics Medical
encyclopedia New York 79(12) 259-32
21 Murray R (1984) Creatinin kaplane et al Clinc Chem Ther CV Mosby Co S Louis
Toronto Princeton 1261-1266 and 418
22 Baggot JD (1978a) Some aspect of clinical pharmacokinetics in veterinary medicine I J
Vet Pharm Ther 1 5-18
23 Baggot JD (1978b) Some aspect of clinical pharmacokinetics in veterinary medicine II
J Vet Pharm Ther 1 111-118
24 Snedecor GW and Cokran WG (1980) Statistical method 7th
Ed The Iowa state
university press Ames Iowa USA 39-63
25 Goudah A Shin HC Shim JH Abd El-Aty AM (2006) Characterization of the
relationship between serum and milk residu disposition of ceftriaxone in lactating ewe J
Vet Pharmacol Ther Aug 29(4) 307-12
26 Jayesh J M Harshad V G Shailesh K B Urvesh D P and Aswin M T (2010)
Pharmacokinetics of ceftriaxone in calves Veterinarski arshiv 80(1) 1-9
wwwwjppscom Vol 5 Issue 01 2016
1455
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
27 Abd-El-Aty AM Goudah A and Abo E S K (2001) Pharmacokinetics
intramuscular bioavailability and tissue residue profiles of ceftazidime in a rabbit
model Dtsch Tierarztl Wochenschr 108(4) 168-171
28 Gardner S Y and Papich M G (2001) Comparison of cefepime pharmacokinetics in
neonatal foals and adult dogs J Vet Pharmacol Therap 24(3) 187-192
29 Ismail M (2005a) Pharmacokinetics of cefepime administered by iv and im routes to
ewes J Vet Pharmacol Therap 28(6) 499-503
30 Patel U D Bhavsar S K and Thaker A M (2006) Pharmacokinetics and dosage
regimen of cefepime following single dose intravenous administration in calves Iran J
Pharmacol Therapeut 5(2) 127-130
31 El-Gendy AAM Tohamy MA and Ismail M (2007) Comparative pharmacokinetic
and renal clearance study of ceftiofur in cross breed friesian and buffalo calves BS Vet
Med J 17(1) 69-77
32 Joshi B and Kumar Sharma S (2009) The pharmacokinetics of cefepime in E coli
lipopolysaccharide induced febrile buffalo calves Veterinarski arhiv 79(6) 523-530
33 Tohamy MA (2008) Pharmacokinetics of ceftiofur sodium administered concomitantly
with dipyrone in healthy and feverish cows J Egypt Soc Pharmacol Exp Ther 29(2)
10-15
34 Rajput N Kumar V D and Sandhu HS (2011) Pharmacokinetics and dosage
regimen of cefpirome in febrile cross-bred calves Iran J Pharmacol Ther 10(1) 17-20
35 Abo-El- Sooud K and Tohamy MA (2011) Comparative pharmacokinetics and milk
concentrations of ceftazidime in healthy and mastitic goats Insight Pharmaceut Sci
1(1) 11-17
36 El-Hewaity M Abd El Latif A Soliman A and Aboubakr M (2014) Comparative
pharmacokinetics of cefquinome (Cobactan 25) following repeated intramuscular
administrations in sheep and goats J Vet Med Doi 949642 1-5
37 El-Sayed M G A El-Komy A A A El barawy A M and Ibrahim D M A (2015)
Pharmacokinetics and tissue residues of ceftiofur in normal and Escherichia coli infected
chickens J Phys Pharm Adv 5(3) 574-582
38 Datta B Mandal TK and Chakraborty A K (2003) Pharmacokinetics of cefotaxime
in goats with experimentally induced kidney damage Ind J pharmacol (35) 173-176
39 Guerrini HV English BP Filippich J L Schneider J and Bourne D W (1986)
The pharmacokinetics of cefotaxime in dog Vet Rec 119(4) 81-83
wwwwjppscom Vol 5 Issue 01 2016
1456
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
40 Atef M Ramadan A Afifi N A and Youssef S A (1990) pharmacokinetic profile
of cefotaxime in goat Res Vet Sci 49(1) 34-38
41 Satish K G Chaudhary RK Srivastiva AK and Garg BD (1990) Pharmacokintics
and dosage regemine of cephalexine in buffulo calves (Bubalis Bubalis following single
intravenous and intramusculer adminsteration Veterinary research commuincation 14
59-62
42 Goudah A (2008) Pharmacokinetic parameters of ceftriaxone after single intravenous
and intramuscular administration in camels (Camelus Dromedarius) Res Vet Sci Jun
84(3) 483-9
43 Sharma SK Srivastava AK and Deore DM (2006) Effect of Ecoli
lipopolysaccharides ndashinduced fever on disposition pattern of cefotaxime in buffalo calves
Veterinarski Arhiv 76(6) 537-545
44 Baggot JD (1977) Priniciple of pharmacokinetics In principle of drug disposition in
domestic animals The physiological Basis of veterinary Clinical Pharmacology 1st ed
WB Saunders Co Philadelphi PA 168-179
45 Karmaker UK Datta BK Patra PH Prashant M Suman S Sar TK Chakaborty
AK and mandal KT (2011) Disposition kinetics of ceftizoxime in healthy and mastitic
goats after intravenous adminsteration Pharmacologyonline 3 935-946
46 Ringger NC Pearson EG Gronwall R Kohlepp S J (1996) Pharmacokinetics of
ceftriaxone in healthy horses Equine Vet J Nov 28(6) 476-9
47 Prawez S Raina R Dimitrova D panka NK Ahanger AA Verma PK (2010) The
pharmacokinetics of cefipime in goats following single dose iv and im adminsteration
Turk j vet Anima Sci 34(5) 427-431
48 Baggot JD (1980) Distribution of antimicrobial agents in normal and diseased animals
JAVMA 19(76) 1085-1090
49 Haddad N S Pedersoli W M Ravis W R Fazeli M H and Carson Jr R L (1985)
Pharmacokinetics of gentamicin at steady-state in ponies serum urine and endometrial
concentrations Am J Vet Res 46(6) 1268-1271
50 Gupta JK Chaudhary RK and Dumka VK (2008) Pharmacokinetics after single
intramuscuker adminsrerarion and in-vitro binding plasma protein of cefoprazone in cross
bred calves Veterinaski Arhiv 78(5) 441-448
51 Al Taher AY (2010) Pharmacokinetics of cefquinome in camels J An Vet Ad 9(4)
848-852
wwwwjppscom Vol 5 Issue 01 2016
1457
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
52 Rajput N Dumka V K and Sandhu HS (2012) Pharmacokinetics and in- vitro
plasma protein binding of cefpirome in cattle Veterinaski Arhiv 82(1) 1-9
53 RebueltoM Albarellos G Ambros L Kreil V Montoya L Bonafine R Otero P
Hallu R (2002) Pharmacokinetics of ceftriaxone administered by the intravenous
intramuscular or subcutaneous routes to dogs J Vet Pharmacol Ther Feb 25(1) 73-6
54 Patel RB Bhavsar SK Solanki PF Patel JH Varia RD Modi Falguni D and
Patel MD (2013) Pharmacokinetics of cefpirome following intravenous and
intramuscular administration in cow calves Sci Int 1(11) 371-374
55 Maradiya J J Goriya H V Bhavsar S K Patel U D and Thaker A M (2010)
Pharmacokinetics of ceftriaxone in calves Veterinarski arhiv 80(1) 1-9
56 Inges R MJ Fillastre J Godin M Leroy A and Humbert G (1982) The
Pharmacokinetics of cefotaxime and its metabolites in subjects with normal and impaired
renal function Clin Infect Dis (4) 379-391
57 Mcelroy D Ravis W R and Clark C H (1986) Pharmacokinetics of cefotaxime in
the domestic cats Am J Vet Res 47(1) 86-88
58 El-Sayed MG Atef M and El-Komy AA (1994) Disposition kinetic of cephradine in
normal and Escherichia coli infected goats Dtsch Tierarztl Wochenschr 101(2) 56-60
59 Soback S and Ziv G (1988) Pharmacokinetics and bioavailability of ceftriaxone
administered intravenously and intramuscularly to calves Am J Vet Res 49 535-538
60 Sharma S K and Srivastava A K (2003) Cefotaxime pharmacokinetics in male
buffalo calves following multiple dosing Veterinarski arhiv 73(4) 191-197
61 Abdulgafar O J Shaibu O B and Emmanuel U E (2011) Effect of Salmonella
typhymurium infection on the pharmacokinetics of ceftriaxone in sokoto red goats Niger
J Basic Applied Sci 19(1) 49-54
62 Ranjan R Birendra K R Amita R and Sanjeet K S (2011) Effect of Effect of E coli E
coli endotoxin induced fever on the pharmacokinetic profile and dosage regimen of
ceftriaxone in sheep (Ovis aries) Veterinarski arhiv 81(4) 423-432
63 Etuk EU and Onyeyili PA (2006) The effect of Salmonella infection on the plasma
kinetic of chloramphenicol in the sokoto red goats Inter J Pharmacol 2(1) 28-32
64 Wang E Bergeron Y and Bergeron MG (2005) Ceftriaxone pharmacokinetics in
interleukin-10-treated murine pneumococcal pneumonia J Antimicrob Chemother 55
721ndash726
wwwwjppscom Vol 5 Issue 01 2016
1458
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
65 El-Sayed MG Hatem ME and El-Komy AA (1989) Disposition kinetic of
gentamicin in normal and endometric cow using microbiological assay Dtsch Tierarztl
Wochenschr 96(8) 412-415
66 Aramyona JJ Mora J Fraile LJ Garcia MA Abadia AR and Breganate MA
(1996) Penetration of enrofloxacin and ciprofloxacin into breast milk and
pharmacokinetics of the drugs in lacating rabbits and neonatal offspring Am J Vet Res
57(4) 547-553
67 Rusmussen F (1966) Studies on the mammary excretion and absorbtion of drugs Vet
Rec (87) 14-18
68 Alkinson A and Begg E (1990) Prediction of drug distribution into human milk from
physicochemical characteristics Clin Pharmacokinet 18(2) 151-167
69 Kenneth F (1997) Drug distribution in human milk Aust Prescr 20(2) 35-40
70 Aleksić M Savić V Popović G Burić N and Kapetanović V (2005) Acidity
constants of cefetamet cefotaxime and ceftriaxone the effect of the substituent at C3
position J Pharm Biomed Anal 39(3-4) 752-756
71 Prades M Brown M P Gronwall R and Miles N S (1988) Pharmacokinetics of
sodium cephapirin in lactating dairy cows Am J Vet Res 49(11) 1888-1890
72 Holazo A A Patel I H Weinfeld R E Konikoff J J and Parsonnet M (1986)
Ceftriaxone pharmacokinetics following multiple intramuscular dosing Euro J Clin
Pharmacol 30(1) 109-112
wwwwjppscom Vol 5 Issue 01 2016
1454
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
13 Gohil P V Patel U D Bhavsar S K Thaker A M (2009) Pharmacokinetics of
ceftriaxone in buffalo calves (Bubalus bubalis) following intravenous and intramuscular
administration Iranian Journal of Veterinary Research 10(1) 33-37
14 Maradyia JJ Harshad VG Shaliesh KB Urvesh DP Aswin MT (2010)
Pharmacokinetics of ceftriaxone in calves Veterinarski arhiv 80(1) 1-9 2010
15 Albarellos GA Kreil VE Landoni MF (2007) Pharmacokinetics of ceftriaxone after
intravenous intramuscular and subcutaneous administration to domestic cats J Vet
Pharmacol Ther Aug 30(4) 345-52
16 Johal B and Srivastava AK (1998) Pharmacokinetics urinary excretion and dosage
regimen of ceftriaxone in Crossbred cow calves 68(10)
17 Otesile EB Ahmed G and Adetosoye AI (1990) Experimental infection of Red Sokoto
goats with Salmonella typhimurium Rev Eacutelev Meacuted Veacutet Pays trop 43(1) 49-53
18 Iroha I R Amadi E S Orji JO and Esimone C O (2008) In vitro evaluation of the
activity of colloidal silver concentrate against Pseudomonas aeruginosa isolated from
postoperative wound infection Scientific Research and Essay May 3(5) 209-211
19 Bennett JV Brodie JL Benner E and Kibry W (1966) Simplified accurate method
for antibiotic assay for clinical specimen Appl Microbial 14 170-175
20 Grove DC and Randall WA (1955) Assay methods of antibiotics Medical
encyclopedia New York 79(12) 259-32
21 Murray R (1984) Creatinin kaplane et al Clinc Chem Ther CV Mosby Co S Louis
Toronto Princeton 1261-1266 and 418
22 Baggot JD (1978a) Some aspect of clinical pharmacokinetics in veterinary medicine I J
Vet Pharm Ther 1 5-18
23 Baggot JD (1978b) Some aspect of clinical pharmacokinetics in veterinary medicine II
J Vet Pharm Ther 1 111-118
24 Snedecor GW and Cokran WG (1980) Statistical method 7th
Ed The Iowa state
university press Ames Iowa USA 39-63
25 Goudah A Shin HC Shim JH Abd El-Aty AM (2006) Characterization of the
relationship between serum and milk residu disposition of ceftriaxone in lactating ewe J
Vet Pharmacol Ther Aug 29(4) 307-12
26 Jayesh J M Harshad V G Shailesh K B Urvesh D P and Aswin M T (2010)
Pharmacokinetics of ceftriaxone in calves Veterinarski arshiv 80(1) 1-9
wwwwjppscom Vol 5 Issue 01 2016
1455
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
27 Abd-El-Aty AM Goudah A and Abo E S K (2001) Pharmacokinetics
intramuscular bioavailability and tissue residue profiles of ceftazidime in a rabbit
model Dtsch Tierarztl Wochenschr 108(4) 168-171
28 Gardner S Y and Papich M G (2001) Comparison of cefepime pharmacokinetics in
neonatal foals and adult dogs J Vet Pharmacol Therap 24(3) 187-192
29 Ismail M (2005a) Pharmacokinetics of cefepime administered by iv and im routes to
ewes J Vet Pharmacol Therap 28(6) 499-503
30 Patel U D Bhavsar S K and Thaker A M (2006) Pharmacokinetics and dosage
regimen of cefepime following single dose intravenous administration in calves Iran J
Pharmacol Therapeut 5(2) 127-130
31 El-Gendy AAM Tohamy MA and Ismail M (2007) Comparative pharmacokinetic
and renal clearance study of ceftiofur in cross breed friesian and buffalo calves BS Vet
Med J 17(1) 69-77
32 Joshi B and Kumar Sharma S (2009) The pharmacokinetics of cefepime in E coli
lipopolysaccharide induced febrile buffalo calves Veterinarski arhiv 79(6) 523-530
33 Tohamy MA (2008) Pharmacokinetics of ceftiofur sodium administered concomitantly
with dipyrone in healthy and feverish cows J Egypt Soc Pharmacol Exp Ther 29(2)
10-15
34 Rajput N Kumar V D and Sandhu HS (2011) Pharmacokinetics and dosage
regimen of cefpirome in febrile cross-bred calves Iran J Pharmacol Ther 10(1) 17-20
35 Abo-El- Sooud K and Tohamy MA (2011) Comparative pharmacokinetics and milk
concentrations of ceftazidime in healthy and mastitic goats Insight Pharmaceut Sci
1(1) 11-17
36 El-Hewaity M Abd El Latif A Soliman A and Aboubakr M (2014) Comparative
pharmacokinetics of cefquinome (Cobactan 25) following repeated intramuscular
administrations in sheep and goats J Vet Med Doi 949642 1-5
37 El-Sayed M G A El-Komy A A A El barawy A M and Ibrahim D M A (2015)
Pharmacokinetics and tissue residues of ceftiofur in normal and Escherichia coli infected
chickens J Phys Pharm Adv 5(3) 574-582
38 Datta B Mandal TK and Chakraborty A K (2003) Pharmacokinetics of cefotaxime
in goats with experimentally induced kidney damage Ind J pharmacol (35) 173-176
39 Guerrini HV English BP Filippich J L Schneider J and Bourne D W (1986)
The pharmacokinetics of cefotaxime in dog Vet Rec 119(4) 81-83
wwwwjppscom Vol 5 Issue 01 2016
1456
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
40 Atef M Ramadan A Afifi N A and Youssef S A (1990) pharmacokinetic profile
of cefotaxime in goat Res Vet Sci 49(1) 34-38
41 Satish K G Chaudhary RK Srivastiva AK and Garg BD (1990) Pharmacokintics
and dosage regemine of cephalexine in buffulo calves (Bubalis Bubalis following single
intravenous and intramusculer adminsteration Veterinary research commuincation 14
59-62
42 Goudah A (2008) Pharmacokinetic parameters of ceftriaxone after single intravenous
and intramuscular administration in camels (Camelus Dromedarius) Res Vet Sci Jun
84(3) 483-9
43 Sharma SK Srivastava AK and Deore DM (2006) Effect of Ecoli
lipopolysaccharides ndashinduced fever on disposition pattern of cefotaxime in buffalo calves
Veterinarski Arhiv 76(6) 537-545
44 Baggot JD (1977) Priniciple of pharmacokinetics In principle of drug disposition in
domestic animals The physiological Basis of veterinary Clinical Pharmacology 1st ed
WB Saunders Co Philadelphi PA 168-179
45 Karmaker UK Datta BK Patra PH Prashant M Suman S Sar TK Chakaborty
AK and mandal KT (2011) Disposition kinetics of ceftizoxime in healthy and mastitic
goats after intravenous adminsteration Pharmacologyonline 3 935-946
46 Ringger NC Pearson EG Gronwall R Kohlepp S J (1996) Pharmacokinetics of
ceftriaxone in healthy horses Equine Vet J Nov 28(6) 476-9
47 Prawez S Raina R Dimitrova D panka NK Ahanger AA Verma PK (2010) The
pharmacokinetics of cefipime in goats following single dose iv and im adminsteration
Turk j vet Anima Sci 34(5) 427-431
48 Baggot JD (1980) Distribution of antimicrobial agents in normal and diseased animals
JAVMA 19(76) 1085-1090
49 Haddad N S Pedersoli W M Ravis W R Fazeli M H and Carson Jr R L (1985)
Pharmacokinetics of gentamicin at steady-state in ponies serum urine and endometrial
concentrations Am J Vet Res 46(6) 1268-1271
50 Gupta JK Chaudhary RK and Dumka VK (2008) Pharmacokinetics after single
intramuscuker adminsrerarion and in-vitro binding plasma protein of cefoprazone in cross
bred calves Veterinaski Arhiv 78(5) 441-448
51 Al Taher AY (2010) Pharmacokinetics of cefquinome in camels J An Vet Ad 9(4)
848-852
wwwwjppscom Vol 5 Issue 01 2016
1457
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
52 Rajput N Dumka V K and Sandhu HS (2012) Pharmacokinetics and in- vitro
plasma protein binding of cefpirome in cattle Veterinaski Arhiv 82(1) 1-9
53 RebueltoM Albarellos G Ambros L Kreil V Montoya L Bonafine R Otero P
Hallu R (2002) Pharmacokinetics of ceftriaxone administered by the intravenous
intramuscular or subcutaneous routes to dogs J Vet Pharmacol Ther Feb 25(1) 73-6
54 Patel RB Bhavsar SK Solanki PF Patel JH Varia RD Modi Falguni D and
Patel MD (2013) Pharmacokinetics of cefpirome following intravenous and
intramuscular administration in cow calves Sci Int 1(11) 371-374
55 Maradiya J J Goriya H V Bhavsar S K Patel U D and Thaker A M (2010)
Pharmacokinetics of ceftriaxone in calves Veterinarski arhiv 80(1) 1-9
56 Inges R MJ Fillastre J Godin M Leroy A and Humbert G (1982) The
Pharmacokinetics of cefotaxime and its metabolites in subjects with normal and impaired
renal function Clin Infect Dis (4) 379-391
57 Mcelroy D Ravis W R and Clark C H (1986) Pharmacokinetics of cefotaxime in
the domestic cats Am J Vet Res 47(1) 86-88
58 El-Sayed MG Atef M and El-Komy AA (1994) Disposition kinetic of cephradine in
normal and Escherichia coli infected goats Dtsch Tierarztl Wochenschr 101(2) 56-60
59 Soback S and Ziv G (1988) Pharmacokinetics and bioavailability of ceftriaxone
administered intravenously and intramuscularly to calves Am J Vet Res 49 535-538
60 Sharma S K and Srivastava A K (2003) Cefotaxime pharmacokinetics in male
buffalo calves following multiple dosing Veterinarski arhiv 73(4) 191-197
61 Abdulgafar O J Shaibu O B and Emmanuel U E (2011) Effect of Salmonella
typhymurium infection on the pharmacokinetics of ceftriaxone in sokoto red goats Niger
J Basic Applied Sci 19(1) 49-54
62 Ranjan R Birendra K R Amita R and Sanjeet K S (2011) Effect of Effect of E coli E
coli endotoxin induced fever on the pharmacokinetic profile and dosage regimen of
ceftriaxone in sheep (Ovis aries) Veterinarski arhiv 81(4) 423-432
63 Etuk EU and Onyeyili PA (2006) The effect of Salmonella infection on the plasma
kinetic of chloramphenicol in the sokoto red goats Inter J Pharmacol 2(1) 28-32
64 Wang E Bergeron Y and Bergeron MG (2005) Ceftriaxone pharmacokinetics in
interleukin-10-treated murine pneumococcal pneumonia J Antimicrob Chemother 55
721ndash726
wwwwjppscom Vol 5 Issue 01 2016
1458
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
65 El-Sayed MG Hatem ME and El-Komy AA (1989) Disposition kinetic of
gentamicin in normal and endometric cow using microbiological assay Dtsch Tierarztl
Wochenschr 96(8) 412-415
66 Aramyona JJ Mora J Fraile LJ Garcia MA Abadia AR and Breganate MA
(1996) Penetration of enrofloxacin and ciprofloxacin into breast milk and
pharmacokinetics of the drugs in lacating rabbits and neonatal offspring Am J Vet Res
57(4) 547-553
67 Rusmussen F (1966) Studies on the mammary excretion and absorbtion of drugs Vet
Rec (87) 14-18
68 Alkinson A and Begg E (1990) Prediction of drug distribution into human milk from
physicochemical characteristics Clin Pharmacokinet 18(2) 151-167
69 Kenneth F (1997) Drug distribution in human milk Aust Prescr 20(2) 35-40
70 Aleksić M Savić V Popović G Burić N and Kapetanović V (2005) Acidity
constants of cefetamet cefotaxime and ceftriaxone the effect of the substituent at C3
position J Pharm Biomed Anal 39(3-4) 752-756
71 Prades M Brown M P Gronwall R and Miles N S (1988) Pharmacokinetics of
sodium cephapirin in lactating dairy cows Am J Vet Res 49(11) 1888-1890
72 Holazo A A Patel I H Weinfeld R E Konikoff J J and Parsonnet M (1986)
Ceftriaxone pharmacokinetics following multiple intramuscular dosing Euro J Clin
Pharmacol 30(1) 109-112
wwwwjppscom Vol 5 Issue 01 2016
1455
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
27 Abd-El-Aty AM Goudah A and Abo E S K (2001) Pharmacokinetics
intramuscular bioavailability and tissue residue profiles of ceftazidime in a rabbit
model Dtsch Tierarztl Wochenschr 108(4) 168-171
28 Gardner S Y and Papich M G (2001) Comparison of cefepime pharmacokinetics in
neonatal foals and adult dogs J Vet Pharmacol Therap 24(3) 187-192
29 Ismail M (2005a) Pharmacokinetics of cefepime administered by iv and im routes to
ewes J Vet Pharmacol Therap 28(6) 499-503
30 Patel U D Bhavsar S K and Thaker A M (2006) Pharmacokinetics and dosage
regimen of cefepime following single dose intravenous administration in calves Iran J
Pharmacol Therapeut 5(2) 127-130
31 El-Gendy AAM Tohamy MA and Ismail M (2007) Comparative pharmacokinetic
and renal clearance study of ceftiofur in cross breed friesian and buffalo calves BS Vet
Med J 17(1) 69-77
32 Joshi B and Kumar Sharma S (2009) The pharmacokinetics of cefepime in E coli
lipopolysaccharide induced febrile buffalo calves Veterinarski arhiv 79(6) 523-530
33 Tohamy MA (2008) Pharmacokinetics of ceftiofur sodium administered concomitantly
with dipyrone in healthy and feverish cows J Egypt Soc Pharmacol Exp Ther 29(2)
10-15
34 Rajput N Kumar V D and Sandhu HS (2011) Pharmacokinetics and dosage
regimen of cefpirome in febrile cross-bred calves Iran J Pharmacol Ther 10(1) 17-20
35 Abo-El- Sooud K and Tohamy MA (2011) Comparative pharmacokinetics and milk
concentrations of ceftazidime in healthy and mastitic goats Insight Pharmaceut Sci
1(1) 11-17
36 El-Hewaity M Abd El Latif A Soliman A and Aboubakr M (2014) Comparative
pharmacokinetics of cefquinome (Cobactan 25) following repeated intramuscular
administrations in sheep and goats J Vet Med Doi 949642 1-5
37 El-Sayed M G A El-Komy A A A El barawy A M and Ibrahim D M A (2015)
Pharmacokinetics and tissue residues of ceftiofur in normal and Escherichia coli infected
chickens J Phys Pharm Adv 5(3) 574-582
38 Datta B Mandal TK and Chakraborty A K (2003) Pharmacokinetics of cefotaxime
in goats with experimentally induced kidney damage Ind J pharmacol (35) 173-176
39 Guerrini HV English BP Filippich J L Schneider J and Bourne D W (1986)
The pharmacokinetics of cefotaxime in dog Vet Rec 119(4) 81-83
wwwwjppscom Vol 5 Issue 01 2016
1456
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
40 Atef M Ramadan A Afifi N A and Youssef S A (1990) pharmacokinetic profile
of cefotaxime in goat Res Vet Sci 49(1) 34-38
41 Satish K G Chaudhary RK Srivastiva AK and Garg BD (1990) Pharmacokintics
and dosage regemine of cephalexine in buffulo calves (Bubalis Bubalis following single
intravenous and intramusculer adminsteration Veterinary research commuincation 14
59-62
42 Goudah A (2008) Pharmacokinetic parameters of ceftriaxone after single intravenous
and intramuscular administration in camels (Camelus Dromedarius) Res Vet Sci Jun
84(3) 483-9
43 Sharma SK Srivastava AK and Deore DM (2006) Effect of Ecoli
lipopolysaccharides ndashinduced fever on disposition pattern of cefotaxime in buffalo calves
Veterinarski Arhiv 76(6) 537-545
44 Baggot JD (1977) Priniciple of pharmacokinetics In principle of drug disposition in
domestic animals The physiological Basis of veterinary Clinical Pharmacology 1st ed
WB Saunders Co Philadelphi PA 168-179
45 Karmaker UK Datta BK Patra PH Prashant M Suman S Sar TK Chakaborty
AK and mandal KT (2011) Disposition kinetics of ceftizoxime in healthy and mastitic
goats after intravenous adminsteration Pharmacologyonline 3 935-946
46 Ringger NC Pearson EG Gronwall R Kohlepp S J (1996) Pharmacokinetics of
ceftriaxone in healthy horses Equine Vet J Nov 28(6) 476-9
47 Prawez S Raina R Dimitrova D panka NK Ahanger AA Verma PK (2010) The
pharmacokinetics of cefipime in goats following single dose iv and im adminsteration
Turk j vet Anima Sci 34(5) 427-431
48 Baggot JD (1980) Distribution of antimicrobial agents in normal and diseased animals
JAVMA 19(76) 1085-1090
49 Haddad N S Pedersoli W M Ravis W R Fazeli M H and Carson Jr R L (1985)
Pharmacokinetics of gentamicin at steady-state in ponies serum urine and endometrial
concentrations Am J Vet Res 46(6) 1268-1271
50 Gupta JK Chaudhary RK and Dumka VK (2008) Pharmacokinetics after single
intramuscuker adminsrerarion and in-vitro binding plasma protein of cefoprazone in cross
bred calves Veterinaski Arhiv 78(5) 441-448
51 Al Taher AY (2010) Pharmacokinetics of cefquinome in camels J An Vet Ad 9(4)
848-852
wwwwjppscom Vol 5 Issue 01 2016
1457
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
52 Rajput N Dumka V K and Sandhu HS (2012) Pharmacokinetics and in- vitro
plasma protein binding of cefpirome in cattle Veterinaski Arhiv 82(1) 1-9
53 RebueltoM Albarellos G Ambros L Kreil V Montoya L Bonafine R Otero P
Hallu R (2002) Pharmacokinetics of ceftriaxone administered by the intravenous
intramuscular or subcutaneous routes to dogs J Vet Pharmacol Ther Feb 25(1) 73-6
54 Patel RB Bhavsar SK Solanki PF Patel JH Varia RD Modi Falguni D and
Patel MD (2013) Pharmacokinetics of cefpirome following intravenous and
intramuscular administration in cow calves Sci Int 1(11) 371-374
55 Maradiya J J Goriya H V Bhavsar S K Patel U D and Thaker A M (2010)
Pharmacokinetics of ceftriaxone in calves Veterinarski arhiv 80(1) 1-9
56 Inges R MJ Fillastre J Godin M Leroy A and Humbert G (1982) The
Pharmacokinetics of cefotaxime and its metabolites in subjects with normal and impaired
renal function Clin Infect Dis (4) 379-391
57 Mcelroy D Ravis W R and Clark C H (1986) Pharmacokinetics of cefotaxime in
the domestic cats Am J Vet Res 47(1) 86-88
58 El-Sayed MG Atef M and El-Komy AA (1994) Disposition kinetic of cephradine in
normal and Escherichia coli infected goats Dtsch Tierarztl Wochenschr 101(2) 56-60
59 Soback S and Ziv G (1988) Pharmacokinetics and bioavailability of ceftriaxone
administered intravenously and intramuscularly to calves Am J Vet Res 49 535-538
60 Sharma S K and Srivastava A K (2003) Cefotaxime pharmacokinetics in male
buffalo calves following multiple dosing Veterinarski arhiv 73(4) 191-197
61 Abdulgafar O J Shaibu O B and Emmanuel U E (2011) Effect of Salmonella
typhymurium infection on the pharmacokinetics of ceftriaxone in sokoto red goats Niger
J Basic Applied Sci 19(1) 49-54
62 Ranjan R Birendra K R Amita R and Sanjeet K S (2011) Effect of Effect of E coli E
coli endotoxin induced fever on the pharmacokinetic profile and dosage regimen of
ceftriaxone in sheep (Ovis aries) Veterinarski arhiv 81(4) 423-432
63 Etuk EU and Onyeyili PA (2006) The effect of Salmonella infection on the plasma
kinetic of chloramphenicol in the sokoto red goats Inter J Pharmacol 2(1) 28-32
64 Wang E Bergeron Y and Bergeron MG (2005) Ceftriaxone pharmacokinetics in
interleukin-10-treated murine pneumococcal pneumonia J Antimicrob Chemother 55
721ndash726
wwwwjppscom Vol 5 Issue 01 2016
1458
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
65 El-Sayed MG Hatem ME and El-Komy AA (1989) Disposition kinetic of
gentamicin in normal and endometric cow using microbiological assay Dtsch Tierarztl
Wochenschr 96(8) 412-415
66 Aramyona JJ Mora J Fraile LJ Garcia MA Abadia AR and Breganate MA
(1996) Penetration of enrofloxacin and ciprofloxacin into breast milk and
pharmacokinetics of the drugs in lacating rabbits and neonatal offspring Am J Vet Res
57(4) 547-553
67 Rusmussen F (1966) Studies on the mammary excretion and absorbtion of drugs Vet
Rec (87) 14-18
68 Alkinson A and Begg E (1990) Prediction of drug distribution into human milk from
physicochemical characteristics Clin Pharmacokinet 18(2) 151-167
69 Kenneth F (1997) Drug distribution in human milk Aust Prescr 20(2) 35-40
70 Aleksić M Savić V Popović G Burić N and Kapetanović V (2005) Acidity
constants of cefetamet cefotaxime and ceftriaxone the effect of the substituent at C3
position J Pharm Biomed Anal 39(3-4) 752-756
71 Prades M Brown M P Gronwall R and Miles N S (1988) Pharmacokinetics of
sodium cephapirin in lactating dairy cows Am J Vet Res 49(11) 1888-1890
72 Holazo A A Patel I H Weinfeld R E Konikoff J J and Parsonnet M (1986)
Ceftriaxone pharmacokinetics following multiple intramuscular dosing Euro J Clin
Pharmacol 30(1) 109-112
wwwwjppscom Vol 5 Issue 01 2016
1456
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
40 Atef M Ramadan A Afifi N A and Youssef S A (1990) pharmacokinetic profile
of cefotaxime in goat Res Vet Sci 49(1) 34-38
41 Satish K G Chaudhary RK Srivastiva AK and Garg BD (1990) Pharmacokintics
and dosage regemine of cephalexine in buffulo calves (Bubalis Bubalis following single
intravenous and intramusculer adminsteration Veterinary research commuincation 14
59-62
42 Goudah A (2008) Pharmacokinetic parameters of ceftriaxone after single intravenous
and intramuscular administration in camels (Camelus Dromedarius) Res Vet Sci Jun
84(3) 483-9
43 Sharma SK Srivastava AK and Deore DM (2006) Effect of Ecoli
lipopolysaccharides ndashinduced fever on disposition pattern of cefotaxime in buffalo calves
Veterinarski Arhiv 76(6) 537-545
44 Baggot JD (1977) Priniciple of pharmacokinetics In principle of drug disposition in
domestic animals The physiological Basis of veterinary Clinical Pharmacology 1st ed
WB Saunders Co Philadelphi PA 168-179
45 Karmaker UK Datta BK Patra PH Prashant M Suman S Sar TK Chakaborty
AK and mandal KT (2011) Disposition kinetics of ceftizoxime in healthy and mastitic
goats after intravenous adminsteration Pharmacologyonline 3 935-946
46 Ringger NC Pearson EG Gronwall R Kohlepp S J (1996) Pharmacokinetics of
ceftriaxone in healthy horses Equine Vet J Nov 28(6) 476-9
47 Prawez S Raina R Dimitrova D panka NK Ahanger AA Verma PK (2010) The
pharmacokinetics of cefipime in goats following single dose iv and im adminsteration
Turk j vet Anima Sci 34(5) 427-431
48 Baggot JD (1980) Distribution of antimicrobial agents in normal and diseased animals
JAVMA 19(76) 1085-1090
49 Haddad N S Pedersoli W M Ravis W R Fazeli M H and Carson Jr R L (1985)
Pharmacokinetics of gentamicin at steady-state in ponies serum urine and endometrial
concentrations Am J Vet Res 46(6) 1268-1271
50 Gupta JK Chaudhary RK and Dumka VK (2008) Pharmacokinetics after single
intramuscuker adminsrerarion and in-vitro binding plasma protein of cefoprazone in cross
bred calves Veterinaski Arhiv 78(5) 441-448
51 Al Taher AY (2010) Pharmacokinetics of cefquinome in camels J An Vet Ad 9(4)
848-852
wwwwjppscom Vol 5 Issue 01 2016
1457
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
52 Rajput N Dumka V K and Sandhu HS (2012) Pharmacokinetics and in- vitro
plasma protein binding of cefpirome in cattle Veterinaski Arhiv 82(1) 1-9
53 RebueltoM Albarellos G Ambros L Kreil V Montoya L Bonafine R Otero P
Hallu R (2002) Pharmacokinetics of ceftriaxone administered by the intravenous
intramuscular or subcutaneous routes to dogs J Vet Pharmacol Ther Feb 25(1) 73-6
54 Patel RB Bhavsar SK Solanki PF Patel JH Varia RD Modi Falguni D and
Patel MD (2013) Pharmacokinetics of cefpirome following intravenous and
intramuscular administration in cow calves Sci Int 1(11) 371-374
55 Maradiya J J Goriya H V Bhavsar S K Patel U D and Thaker A M (2010)
Pharmacokinetics of ceftriaxone in calves Veterinarski arhiv 80(1) 1-9
56 Inges R MJ Fillastre J Godin M Leroy A and Humbert G (1982) The
Pharmacokinetics of cefotaxime and its metabolites in subjects with normal and impaired
renal function Clin Infect Dis (4) 379-391
57 Mcelroy D Ravis W R and Clark C H (1986) Pharmacokinetics of cefotaxime in
the domestic cats Am J Vet Res 47(1) 86-88
58 El-Sayed MG Atef M and El-Komy AA (1994) Disposition kinetic of cephradine in
normal and Escherichia coli infected goats Dtsch Tierarztl Wochenschr 101(2) 56-60
59 Soback S and Ziv G (1988) Pharmacokinetics and bioavailability of ceftriaxone
administered intravenously and intramuscularly to calves Am J Vet Res 49 535-538
60 Sharma S K and Srivastava A K (2003) Cefotaxime pharmacokinetics in male
buffalo calves following multiple dosing Veterinarski arhiv 73(4) 191-197
61 Abdulgafar O J Shaibu O B and Emmanuel U E (2011) Effect of Salmonella
typhymurium infection on the pharmacokinetics of ceftriaxone in sokoto red goats Niger
J Basic Applied Sci 19(1) 49-54
62 Ranjan R Birendra K R Amita R and Sanjeet K S (2011) Effect of Effect of E coli E
coli endotoxin induced fever on the pharmacokinetic profile and dosage regimen of
ceftriaxone in sheep (Ovis aries) Veterinarski arhiv 81(4) 423-432
63 Etuk EU and Onyeyili PA (2006) The effect of Salmonella infection on the plasma
kinetic of chloramphenicol in the sokoto red goats Inter J Pharmacol 2(1) 28-32
64 Wang E Bergeron Y and Bergeron MG (2005) Ceftriaxone pharmacokinetics in
interleukin-10-treated murine pneumococcal pneumonia J Antimicrob Chemother 55
721ndash726
wwwwjppscom Vol 5 Issue 01 2016
1458
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
65 El-Sayed MG Hatem ME and El-Komy AA (1989) Disposition kinetic of
gentamicin in normal and endometric cow using microbiological assay Dtsch Tierarztl
Wochenschr 96(8) 412-415
66 Aramyona JJ Mora J Fraile LJ Garcia MA Abadia AR and Breganate MA
(1996) Penetration of enrofloxacin and ciprofloxacin into breast milk and
pharmacokinetics of the drugs in lacating rabbits and neonatal offspring Am J Vet Res
57(4) 547-553
67 Rusmussen F (1966) Studies on the mammary excretion and absorbtion of drugs Vet
Rec (87) 14-18
68 Alkinson A and Begg E (1990) Prediction of drug distribution into human milk from
physicochemical characteristics Clin Pharmacokinet 18(2) 151-167
69 Kenneth F (1997) Drug distribution in human milk Aust Prescr 20(2) 35-40
70 Aleksić M Savić V Popović G Burić N and Kapetanović V (2005) Acidity
constants of cefetamet cefotaxime and ceftriaxone the effect of the substituent at C3
position J Pharm Biomed Anal 39(3-4) 752-756
71 Prades M Brown M P Gronwall R and Miles N S (1988) Pharmacokinetics of
sodium cephapirin in lactating dairy cows Am J Vet Res 49(11) 1888-1890
72 Holazo A A Patel I H Weinfeld R E Konikoff J J and Parsonnet M (1986)
Ceftriaxone pharmacokinetics following multiple intramuscular dosing Euro J Clin
Pharmacol 30(1) 109-112
wwwwjppscom Vol 5 Issue 01 2016
1457
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
52 Rajput N Dumka V K and Sandhu HS (2012) Pharmacokinetics and in- vitro
plasma protein binding of cefpirome in cattle Veterinaski Arhiv 82(1) 1-9
53 RebueltoM Albarellos G Ambros L Kreil V Montoya L Bonafine R Otero P
Hallu R (2002) Pharmacokinetics of ceftriaxone administered by the intravenous
intramuscular or subcutaneous routes to dogs J Vet Pharmacol Ther Feb 25(1) 73-6
54 Patel RB Bhavsar SK Solanki PF Patel JH Varia RD Modi Falguni D and
Patel MD (2013) Pharmacokinetics of cefpirome following intravenous and
intramuscular administration in cow calves Sci Int 1(11) 371-374
55 Maradiya J J Goriya H V Bhavsar S K Patel U D and Thaker A M (2010)
Pharmacokinetics of ceftriaxone in calves Veterinarski arhiv 80(1) 1-9
56 Inges R MJ Fillastre J Godin M Leroy A and Humbert G (1982) The
Pharmacokinetics of cefotaxime and its metabolites in subjects with normal and impaired
renal function Clin Infect Dis (4) 379-391
57 Mcelroy D Ravis W R and Clark C H (1986) Pharmacokinetics of cefotaxime in
the domestic cats Am J Vet Res 47(1) 86-88
58 El-Sayed MG Atef M and El-Komy AA (1994) Disposition kinetic of cephradine in
normal and Escherichia coli infected goats Dtsch Tierarztl Wochenschr 101(2) 56-60
59 Soback S and Ziv G (1988) Pharmacokinetics and bioavailability of ceftriaxone
administered intravenously and intramuscularly to calves Am J Vet Res 49 535-538
60 Sharma S K and Srivastava A K (2003) Cefotaxime pharmacokinetics in male
buffalo calves following multiple dosing Veterinarski arhiv 73(4) 191-197
61 Abdulgafar O J Shaibu O B and Emmanuel U E (2011) Effect of Salmonella
typhymurium infection on the pharmacokinetics of ceftriaxone in sokoto red goats Niger
J Basic Applied Sci 19(1) 49-54
62 Ranjan R Birendra K R Amita R and Sanjeet K S (2011) Effect of Effect of E coli E
coli endotoxin induced fever on the pharmacokinetic profile and dosage regimen of
ceftriaxone in sheep (Ovis aries) Veterinarski arhiv 81(4) 423-432
63 Etuk EU and Onyeyili PA (2006) The effect of Salmonella infection on the plasma
kinetic of chloramphenicol in the sokoto red goats Inter J Pharmacol 2(1) 28-32
64 Wang E Bergeron Y and Bergeron MG (2005) Ceftriaxone pharmacokinetics in
interleukin-10-treated murine pneumococcal pneumonia J Antimicrob Chemother 55
721ndash726
wwwwjppscom Vol 5 Issue 01 2016
1458
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
65 El-Sayed MG Hatem ME and El-Komy AA (1989) Disposition kinetic of
gentamicin in normal and endometric cow using microbiological assay Dtsch Tierarztl
Wochenschr 96(8) 412-415
66 Aramyona JJ Mora J Fraile LJ Garcia MA Abadia AR and Breganate MA
(1996) Penetration of enrofloxacin and ciprofloxacin into breast milk and
pharmacokinetics of the drugs in lacating rabbits and neonatal offspring Am J Vet Res
57(4) 547-553
67 Rusmussen F (1966) Studies on the mammary excretion and absorbtion of drugs Vet
Rec (87) 14-18
68 Alkinson A and Begg E (1990) Prediction of drug distribution into human milk from
physicochemical characteristics Clin Pharmacokinet 18(2) 151-167
69 Kenneth F (1997) Drug distribution in human milk Aust Prescr 20(2) 35-40
70 Aleksić M Savić V Popović G Burić N and Kapetanović V (2005) Acidity
constants of cefetamet cefotaxime and ceftriaxone the effect of the substituent at C3
position J Pharm Biomed Anal 39(3-4) 752-756
71 Prades M Brown M P Gronwall R and Miles N S (1988) Pharmacokinetics of
sodium cephapirin in lactating dairy cows Am J Vet Res 49(11) 1888-1890
72 Holazo A A Patel I H Weinfeld R E Konikoff J J and Parsonnet M (1986)
Ceftriaxone pharmacokinetics following multiple intramuscular dosing Euro J Clin
Pharmacol 30(1) 109-112
wwwwjppscom Vol 5 Issue 01 2016
1458
Kaur et al World Journal of Pharmacy and Pharmaceutical Sciences
65 El-Sayed MG Hatem ME and El-Komy AA (1989) Disposition kinetic of
gentamicin in normal and endometric cow using microbiological assay Dtsch Tierarztl
Wochenschr 96(8) 412-415
66 Aramyona JJ Mora J Fraile LJ Garcia MA Abadia AR and Breganate MA
(1996) Penetration of enrofloxacin and ciprofloxacin into breast milk and
pharmacokinetics of the drugs in lacating rabbits and neonatal offspring Am J Vet Res
57(4) 547-553
67 Rusmussen F (1966) Studies on the mammary excretion and absorbtion of drugs Vet
Rec (87) 14-18
68 Alkinson A and Begg E (1990) Prediction of drug distribution into human milk from
physicochemical characteristics Clin Pharmacokinet 18(2) 151-167
69 Kenneth F (1997) Drug distribution in human milk Aust Prescr 20(2) 35-40
70 Aleksić M Savić V Popović G Burić N and Kapetanović V (2005) Acidity
constants of cefetamet cefotaxime and ceftriaxone the effect of the substituent at C3
position J Pharm Biomed Anal 39(3-4) 752-756
71 Prades M Brown M P Gronwall R and Miles N S (1988) Pharmacokinetics of
sodium cephapirin in lactating dairy cows Am J Vet Res 49(11) 1888-1890
72 Holazo A A Patel I H Weinfeld R E Konikoff J J and Parsonnet M (1986)
Ceftriaxone pharmacokinetics following multiple intramuscular dosing Euro J Clin
Pharmacol 30(1) 109-112