volume distribution

7/23/2019 volume distribution

http://slidepdf.com/reader/full/volume-distribution 1/24

Volume Distribution



CONCEPT OF VOLUME OF DISTRIBUTION OF DRUGS:

DEFINITION OF VD

Add DRUG

to Beaker

Calculate Volume

Ota!" Sam#le

A$$a% &or 'Dru()

*St!r+

'Dru() , Amou"t Added Volume o& Beaker

Volume o& Beaker , Amou"t Added 'Dru()



Distribution. ¿Where do drugs go?



CONCEPT OF VOLUME OF DISTRIBUTION OF DRUGS:

DEFINITION OF VD

Do$e Bod%

-!t. DRUG

Calculate Volume

*T.!$ /olume !$ called VD

+

Ota!" Pla$ma Sam#le

A$$a% &or 'D)P

B% DEFINITION: VD , A0'D)P

*-.ere A !$ amou"t o& dru( !" od% a"d 'D)P !$ co"ce"trat!o" o& dru( !" #la$ma+



Volume of distribution

Relative size of various

distribution volumeswithin a 70-kgindividual

• Interstitial fuid

represents about15% of the• total body weight.

• Intracellular fuid (fuid inside cells) -40% of

• the total bodyweight.

• Blood plasma - 8% of the body weight.

http://pharmamotion.com.ar



lasma !ompartment

• Vd" around # $.

• Very high mole!ular

weight drugs% ordrugsthat bind to plasmaproteins e&!esively

• '&ample" heparin ($ )*-#+




'&tra!ellular ,uid

Vd" between (and ( $.

Drugs that havea low mole!ularweight but arehydrophili!.

'&ample

tra!uronium $ )/-#+




Vd eual or higher than totalbody water

• Di1usion to intra!elullar ,uid .Vd eual to total body water.

– 'thanol */ $ )*(-(+ – lfentanyl #2 $ )*#-77+

• Drug that binds strongly totissues. Vd higher than total

body water. – 3entanyl" 4/0 $

– ropofol" #20 $

– Digo&in"*/# $



5hy does Vd di1erent for ea!h drug6



• he rate of delivery and potentialamount of drug distributed into

tissues depends on8

• 9ardia! output% Regional blood ,ow%

9apillary permeability and tissuevolume.

•5ell-perfused organs (liver, kidney,

brain initially re!eive most of thedrug•$esser perfused" delivery to muscle,

most viscera, skin, and !at is



"istribution

• determines the transport of drugs to their site of a!tion% to othersites% andto the organs of metabolism ande&!retion.

Not uniorm8

Di1eren!e in per!usion rates#

$enetrate - !apillary endothelium.



&olume o! "istribution (&d

• values range from about #: of body volume to as high as (00 $.

• he latter ;gure is mu!h higher than anyone<s total volume% so &d is an

arti'cial concept#

• =mportan!e - it will predi!t whether the drug will reside in te blood orin te tissue#

• )ater soluble dru*s +ill reside in te blood, and !at solubledru*s +ill reside in cell membranes, adipose tissue and oter

!at-ric areas#• Volume of Distribution also relates to whether a drug is 3ree > protein

bound

• Drugs that are !harged tend to bind to serum proteins.

• rotein bound drugs form ma!romole!ular !omple&es tat cannotcross biolo*ical membranes and remain con'ned to te

bloodstream#• $atolo*ical states may also !hange Vd.

• ?e!ause Vd mathemati!ally relates blood !on!entration to dosage it may

be employed in interpretation o! laboratory results.• @seful for providing an estimate o! dosa*e% it follows that it !an help

estimate the amount of antidote to be given.

• =ndi!ate whether there is any value in trying to enhan!e elimination as%for e&ample% by dialysis.



Volume of distribution

• pparent and hypotheti!al volume inwhi!h the drug is dispersed.

ionconcentratPlasmaDose=Vd

• Why is it relevant?

• To calculate the loading dose of a drug




Volume of Distribution

• Vd is helpful in the !onte&t of drugmonitoring.

• redi!ts whether the pra!ti!e of drugmeasurement in blood will have any!lini!al value.

• sy!hotropi! drugs su!h as tranuilizers%antidepressants% antipsy!hoti!s% mood-altering agents%et!.% !reate their e1e!ts by binding atsites within the !entral nervous system.



• pysician +ants to administer ananestetic a*ent at a rate o! m*.rby I& in!usion# /e elimination rate

constant is 0#1 r0

1

, and te volumeo! distribution (one compartment is10 # )at loadin* dose sould berecommended i! te dru* level to

reac 2*.m immediately3

Problem no 4



iven, in!usion rate m*.r

elimination rate 0#1 r 1

volume o! distribution 10

6e7uired concentration 2*.m

oadin* dose &d 9ss

1000m 2*.m

000 2*

0m*

:ere +e can calculate " usin* in!usion rate and elimination rateas +ell #



Reference books say the V d of theophylline

is 0.5 L per kg of body weight.

What is the IV loading dose to give a serumtheophylline concentration of ! mg"L ina #! kg man$

=W VC or LD = C p V d

LD = (12 mg/L) (0.5 L/kg) (62 kg) = 372 mg we usually use mcg"mL %or ug"mL&' which is the same thing as mg"L



(ctually' theophylline for in)ection is avail*able only as (minophylline

%theophylline+ethylenediamine&' which contains,0- theophylline. In this problem' we needto give a larger weight of (minophylline toget the same weight of theophylline.

/! mg heo

0.,01 2#5 mg (mino

his gives us a loading dose



Question

• 5hat is the loading dose reuired fordrug if8

• arget !on!entration is 0 mg>$

• Vd is 0.7# $>kg

• atients weight is 7# kg

• Answer is on the next slide



Answer: Loading Dose of Drug A

• Dose A arget 9on!entration & VD

• Vd A 0.7# $>kg & 7# kg A #2.4# $

• arget 9on!. A 0 mg>$

• Dose A 0 mg>$ & #2.4# $ A #2# mg

• his would probably be rounded to #20 oreven #00 mg

volume distribution

Documents