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DETERMINATION OF IQB-9302 LEVELS IN BEAGLE DOG PLASMA
Sponsor:Laboratorios INIBSA
Crta de Sabadell a Granollers, Km.14.508185 Lliça de Vall (Barcelona)
Spain
T.P.S. Study No.:616C-503-532-98
Contract Laboratory:T.P.S., Inc.
10424 Middle Mt. Vernon Rd.Mt. Vernon, IN 47620
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TABLE OF CONTENTS
Page #TABLE OF CONTENTS 2
SIGNATURE PAGE 3
QUALITY ASSURANCE STATEMENT 4
INTRODUCTION 5
MATERIALS 5
ASSAY PROCEDURE 7
RESULTS AND DISCUSSION 8
REFERENCES 9
TABLE 1 Back Calculated Results and Regression Statistics forIQB-9302 Calibration Standards 10
TABLE 2 Quality Control Results and Statistics 11
TABLE 3 Schedule of Batches Assayed 12
FIGURE 1 Representative Calibration Curve (Batch R09R) 13
FIGURE 2 Representative Chromatograms of Study and QualityControl Samples 14
APPENDIX A IQB-9302 Plasma Concentrations 15
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SIGNATURE PAGE
Work done by: P.A. Downing, B.A. S.E. Blessinger, BSMT(ASCP)
Reported by: Philip A. Downing, B.A. DateAnalytical Chemistry Manager
Approved by: Lisa J. Clare, D.V.M. DateStudy Director
James A. Botta, Jr., D.V.M., Ph.D. DateVice President of Research andDevelopment
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QUALITY ASSURANCE REVIEW STATEMENT
The Study 616C-503-532-98 plasma analysis report has been reviewed for format andcontent by the Quality Assurance Unit. The material contained herein has been accepted asan accurate and true representation of the data and procedures contained in the study.
Quality Assurance audits of this report were conducted by the Quality Assurance Unit andreported to the study director and management.
Deborah G. Fehrenbacher, B.S., MT(ASCP) DateQuality Assurance Auditor
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1.0 INTRODUCTION
The analysis of 430 beagle dog plasma samples for IQB-9302 concentrations hasbeen performed by T.P.S., Inc. Plasma samples from the study (T.P.S. Study No.:616C-503-532-98, Sponsor Study No.: 032b) were collected on 11-10-98 and 12-7-98 and stored frozen until analyzed for IQB-9302 using a validated HPLC method.
2.0 MATERIALS
2.1 Equipment/Materials
2.1.1 Equipment used in the procedure:
A. 1 mL volumetric class “A” pipetB. 5, 10, 25 and 100 mL volumetric class “A” flasksC. 1000 mL volumetric cylinderD. Adjustable Eppendorf pipetE. Adjustable Eppendorf repeating pipetF. Fisher Scientific Accumet® Model 220 pH MeterG. Vac-Elut solid phase extraction vacuum apparatusH. Multi-tube vortexer – Dade International Inc.I. 200 µL limited volume inserts with starburst capsJ. Glass 12x75 mm test tubes
2.1.2 HPLC system included the following components:
A. Waters µBondapak® C18 reverse phase column (3.9 x 300 mm, 10µm particle size)B. Phenomenex® Security GuardTM guard column with C18
(4.0 x 3.0 mm) cartridgeC. Waters Oasis® MCX 1 cc/30 mg SPE cartridgeD. Waters Model 600E multisolvent delivery systemE. Waters Model 712 WISP automatic sample injectorF. Waters Model 490 multi-wavelength detectorG. Chrom Perfect (version 3.08) chromatography software
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2.2 Reagents
A. IQB-9302.HCl, Lot No. 9454/R.E-1, Purity = 100.7%(1.1249 free base correction factor) - Laboratorios INIBSA,Spain
B. Bupivacaine HCl, Lot No. 117H0875, Purity = >99.9% -Sigma Chemical Company
C. Water, HPLC Grade – Fisher ScientificD. Sodium Phosphate Monobasic, ACS Certified – Fisher ScientificE. Sodium Hydroxide Solution, 50% w/w – Fisher ScientificF. Methanol (MeOH), HPLC Grade – Fisher ScientificG. Acetonitrile (ACN), HPLC Grade – Fisher ScientificH. Ammonium Hydroxide (NH4OH), ACS Certified – Fisher
ScientificI. o-Phosphoric Acid 85%, HPLC Grade – Fisher ScientificJ. 0.1N Hydrochloric Acid Solution – Fisher ScientificK. Blank dog plasma – T.P.S., Inc. (collected in-house from
untreated beagle dogs)
2.3 Calibration Standards
Calibration standards (Lot No. CC01) were prepared on 11-09-99 atconcentrations of 50, 100, 250, 500, 1000, 2000, 5000 ng/mL (free base)by fortifying blank dog beagle plasma with IQB-9302. Aliquots of eachlevel were frozen following preparation.
2.4 Quality Control Samples
Quality control (QC) samples (Lot No. QC01) were prepared on 11-09-99at three different levels (150, 750, 2500 ng/mL – free base) by fortifyingblank dog beagle plasma with IQB-9302. Aliquots of each level werefrozen following preparation.
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3.0 ASSAY PROCEDURE
3.1 Sample Preparation
A. Transferred 0.50 mL of each standard, QC, and sample toseparate labeled glass test tubes.
B. Pipetted 25 µL of 2.0% phosphoric acid and 0.50 mL ofinternal standard (2 µg/mL) to each tube and briefly vortexed.(Note: 0.5 mL of water was added to the plasma blankstandards instead of internal standard.)
C. Conditioned SPE cartridges with 2 (1 mL) aliquots ofMeOH followed by 2 (1 mL) aliquots of water.
D. Transferred samples to SPE cartridges.D. Washed remaining sample from each test tube using 1 mL
of 0.1N HCl and then transferred wash to SPE cartridges.F. Washed SPE cartridges with 1 mL of 0.1N HCl.G. Washed SPE cartridges with 2 (1 mL) aliquots of MeOH.H. Extracted analytes with 2 (1 mL) aliquots of 5% NH4OH in
MeOH. Extract was collected in clean glass test tubes.I. Extract was dried under nitrogen at approximately 50°C.
J. Reconstituted with 150 µL of mobile phase A and vortexedon a multi-tube vortexer for approximately 15 minutes.
K. Transferred samples to 200 µL limited volume inserts withstarburst caps.
3.2 Chromatographic Conditions
IQB-9302 was separated on a Waters µBondapak® C-18 reverse-phasecolumn with a mobile phase of MeOH:ACN:0.02M phosphate buffer,pH=6, (15:40:45, v/v/v) at a flow rate of 1.2 mL/min at ambientconditions. Injections of 100µL were made by the WISP and a run time of25 minutes per injection was used. The 600 series pump was programmedto wash the column for approximately 2.5 minutes using 85%ACN inwater following the elution of the internal standard. The detector was setat a wavelength of 210 nm and an AUFS of 0.30
3.3 Data handling
All chromatographic data was collected using Chrom Perfect (version3.08) chromatographic software. A method, sequence file, and calibrationfile were constructed and downloaded prior to the injection of the firstsample. For each assay day, a standard curve was constructed by plotting
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peak area ratios for IQB-9302/Internal Standard versus the respectivestandard concentration. Sample concentrations were determinedmathematically by comparison of the peak area ratios in the sample to theweighted (1/x) regression equation obtained from the standards data.
4.0 RESULTS AND DISCUSSION
4.1 Standards
Table 1 contains results of the standard curves obtained during theanalysis of study samples. Calibration standards where analyzed induplicate (singlet when the number of study samples was less than 25)Correlation coefficients ranged from 0.997-1.00). The mean calculatedrelative standard deviation (% RSD) for the back-calculatedconcentrations of the calibration standards ranged from 2.9 to 8.3. Thepercent deviation (% Dev.) was determined be comparing the back-calculated concentrations to the theoretical concentration for eachrespective standard. The mean percent deviations ranged from –2.2 to 1.7.Figure 1 shows a representative standard calibration curve plotted usingChrom Perfect software from Batch R09R.
4.2 Quality Control Samples
Results of the analysis of QCs are shown in Table 2. QC samples whereanalyzed in duplicate (singlet when the number of study samples was lessthan 25) at 3 levels. The mean calculated relative standard deviation (%RSD) for the back-calculated concentrations of the low, middle, and highQC pools were 6.0, 4.6, 3.8, respectively. The percent deviation (% Dev.)was determined be comparing the back-calculated concentrations to thetheoretical concentration for each respective standard. The mean percentdeviation for the low, middle, and high QC pools were 2.8, 2.3, and 0.5,respectively.
4.3 Assay Performance
Samples were analyzed over 10 acceptable runs (the tenth run includedrepeat samples). Acceptability of each run was determined as follows:four of the six QC samples must pass a 20 % maximum bias acceptancecriteria for the low, middle, and high pools with no more than one QCsample at any concentration failing the acceptance criteria. Calibrationstandards must also pass the 20 % maximum bias acceptance criteria foreach level with no more than 25 % of the standards failing the criteria (SeeTable 3). Ten runs passed the above mentioned acceptance criteria. One
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run (R04R) was rejected due to pump failure during the run and samplesre-extracted and analyzed in run R04XR.
4.5 Sample Analysis
Study samples were randomized prior to analyzing. Samples were storedfrozen and allowed to thaw-out at room temperature prior to aliquoting.Samples were re-frozen after aliquoting. Eleven samples were re-analyzeddue to improper integration.
Figure 2 contains representative chromatograms of study samples and QC:Group #4 – Day 28 - predose (Animal BKG4M03), Group #3 - Day 1 –1.5 hour (Animal BKG3F01), Group # 3 - Day 1 - 5 min. (AnimalBKG3F01), and mid-level QC (750 ng/mL).
5.0 REFERENCES
Downing, P.A., Validation of a High Performance Liquid Chromatographic Assayfor IQB-9302 in Dog Plasma, T.P.S., Inc., June 16. 1999
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TABLE 1
Back Calculated Results and Regression Statistics for IQB-9302 CalibrationStandards
Batch STD#1
STD#2
STD#3
STD#4
STD#5
STD#6
STD#7
Y-intercept r-factor
R01R 54.969.0*
100101
244253
481517
9061018
19231973
49405240
-0.009 0.998
R02R 53.549.7
10195.4
251254
467704*
10021021
19721999
48645171
-0.004 0.999
R03R 52.153.5
97.0106
241245
485493
9911012
17592065
50365164
-0.003 0.998
R04XR 48.950.8
91.8126*
245272
478545
9411118
19231865
52304892
-0.004 0.997
R05R 15.4*53.8
10099.8
249245
498519
985966
18022060
50535119
-0.0002 0.998
R06R 41.056.4
80.687.1
297293
404488
11251111
19312169
47934922
-0.003 0.997
R07R 51.746.2
101101
244247
503514
10001027
1613*3540*
47535211
-0.002 0.997
R08R 53.364.3*
10993.1
239248
495499
9871013
19391970
50015103
-0.011 1.00
R09R 43.453.7
92.6103
251268
495528
9921018
19152020
49455075
-0.001 1.00
R10R 50.7 101 247 498 999 1971 5033 -0.009 1.00N 16 18 19 18 19 17 19
Nominal(ng/mL)
50 100 250 500 1000 2000 5000
Mean 50.9 97.8 254 495 1012 1956 5029Std. Dev. 4.21 6.80 16.5 29.5 55.4 97.0 145% RSD 8.3 7.0 6.5 6.0 5.5 5.0 2.9% Dev. 1.7 -2.2 1.7 -1.0 1.2 -2.2 0.6
* Standard dropped due to out-of-range value (±20 %)
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TABLE 2
Quality Control Results and Statistics
Batch LQC MQC HQCR01R 147
164765741747
24652462
R02R 160152
755775
25312613
R03R 147146
770771
24722570
R04XR 150164
712760
23802484
R05R 148173
805817
26222774
R06R 139219*
708737
24852618
R07R 148157
841787
25492502
R08R 165163
819801
23872420
R09R 142159
720752772
24672428
R10R 151 761 2525N 18 21 19
Nominal (ng/mL) 150 750 2500Mean 154 767 2513
Std. Dev. 9.28 35.3 96.0% RSD 6.0 4.6 3.8% Dev. 2.8 2.3 0.5
* QC dropped due to out-of-range value (±20 %)
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TABLE 3
Schedule of Batches Assayed
Batch # Date Extracted Status
R01R 11-15-99 AcceptedR02R 11-17-99 AcceptedR03R 11-22-99 AcceptedR04R 11-24-99 Failed *
R04XR 11-30-99 AcceptedR05R 12-6-99 AcceptedR06R 12-8-99 AcceptedR07R 12-10-99 AcceptedR08R 12-13-99 AcceptedR09R 12-15-99 AcceptedR10R 12-17-99 Accepted
* Batch R04R was rejected due to pump failure during the run. Samples were re-extractedand assayed in Batch R04XR.
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APPENDIX A
IQB-9302 Plasma Concentrations
Dosage Key
GroupNumber
TestArticle
Dose(mg/kg/day)
Dose Volume(mL/kg)
Number ofAnimals
Males FemalesBKG1* Vehicle 0 1 5 5BKG2 IQB-9302 1 1 5 5BKG3 IQB-9302 2 1 5 5BKG4 IQB-9302 3 1 5 5
* Only predose samples were collected from Group BKG1
Report Code Key
B = Below Quantifiable Limits (< 50 ng/mL)N = None Detected
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Group BKG1 (0 mg/kg/day): IQB-9302 Plasma Concentrationsin Male Beagle Dogs
Day 1
Collection Interval Animal Number Concentration (ng/mL)
Predose BKG1M 1 N BKG1M 2 N BKG1M 3 N BKG1M 4 N BKG1M 5 N
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Group BKG2 (1 mg/kg/day): IQB-9302 Plasma Concentrationsin Male Beagle Dogs
Day 1
Collection Interval Animal Number Concentration (ng/mL)
Predose BKG2M 1 N BKG2M 2 N BKG2M 3 N BKG2M 4 N BKG2M 5 N
5 min BKG2M 1 1762 BKG2M 2 1943 BKG2M 3 1249 BKG2M 4 1142 BKG2M 5 2045
15 min BKG2M 1 1045 BKG2M 2 1194 BKG2M 3 753 BKG2M 4 738 BKG2M 5 1135
30 min BKG2M 1 578 BKG2M 2 533 BKG2M 3 394 BKG2M 4 386 BKG2M 5 537
1 hour BKG2M 1 173 BKG2M 2 143 BKG2M 3 125 BKG2M 4 123 BKG2M 5 131
1.5 hour BKG2M 1 B BKG2M 2 B BKG2M 3 B BKG2M 4 57.1 BKG2M 5 51.3
3 hour BKG2M 1 N BKG2M 2 N BKG2M 3 N BKG2M 4 N BKG2M 5 N
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Group BKG3 (2 mg/kg/day): IQB-9302 Plasma Concentrationsin Male Beagle Dogs
Day 1
Collection Interval Animal Number Concentration (ng/mL)
Predose BKG3M 1 N BKG3M 2 N BKG3M 3 N BKG3M 4 N BKG3M 5 N
5 min BKG3M 1 2652 BKG3M 2 1145 BKG3M 3 1876 BKG3M 4 2054 BKG3M 5 1829
15 min BKG3M 1 2168 BKG3M 2 967 BKG3M 3 1358 BKG3M 4 1463 BKG3M 5 1498
30 min BKG3M 1 1274 BKG3M 2 686 BKG3M 3 762 BKG3M 4 890 BKG3M 5 755
1 hour BKG3M 1 491 BKG3M 2 330 BKG3M 3 201 BKG3M 4 366 BKG3M 5 240
1.5 hour BKG3M 1 272 BKG3M 2 150 BKG3M 3 B BKG3M 4 67.1 BKG3M 5 80.8
3 hour BKG3M 1 N BKG3M 2 N BKG3M 3 N BKG3M 4 N BKG3M 5 N
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Group BKG4 (3 mg/kg/day): IQB-9302 Plasma Concentrationsin Male Beagle Dogs
Day 1
Collection Interval Animal Number Concentration (ng/mL)
Predose BKG4M 1 N BKG4M 2 N BKG4M 3 N BKG4M 4 N BKG4M 5 N
5 min BKG4M 1 3507 BKG4M 2 2892 BKG4M 3 3297 BKG4M 4 2517 BKG4M 5 2045
15 min BKG4M 1 2273 BKG4M 2 1573 BKG4M 3 2186 BKG4M 4 1561 BKG4M 5 1574
30 min BKG4M 1 1020 BKG4M 2 799 BKG4M 3 1674 BKG4M 4 1130 BKG4M 5 1121
1 hour BKG4M 1 296 BKG4M 2 209 BKG4M 3 814 BKG4M 4 518 BKG4M 5 521
1.5 hour BKG4M 1 108 BKG4M 2 71.3 BKG4M 3 299 BKG4M 4 193 BKG4M 5 287
3 hour BKG4M 1 N BKG4M 2 N BKG4M 3 N BKG4M 4 N BKG4M 5 B
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Group BKG1 (0 mg/kg/day): IQB-9302 Plasma Concentrationsin Female Beagle Dogs
Day 1
Collection Interval Animal Number Concentration (ng/mL)
Predose BKG1F 1 N BKG1F 2 N BKG1F 3 N BKG1F 4 N BKG1F 5 N
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Group BKG2 (1 mg/kg/day): IQB-9302 Plasma Concentrationsin Female Beagle Dogs
Day 1
Collection Interval Animal Number Concentration (ng/mL)
Predose BKG2F 1 N BKG2F 2 N BKG2F 3 N BKG2F 4 N BKG2F 5 N
5 min BKG2F 1 1651 BKG2F 2 1227 BKG2F 3 1356 BKG2F 4 1682 BKG2F 5 1793
15 min BKG2F 1 871 BKG2F 2 598 BKG2F 3 838 BKG2F 4 1144 BKG2F 5 981
30 min BKG2F 1 407 BKG2F 2 282 BKG2F 3 466 BKG2F 4 556 BKG2F 5 411
1 hour BKG2F 1 124 BKG2F 2 62.2 BKG2F 3 143 BKG2F 4 136 BKG2F 5 110
1.5 hour BKG2F 1 N BKG2F 2 N BKG2F 3 B BKG2F 4 B BKG2F 5 B
3 hour BKG2F 1 N BKG2F 2 N BKG2F 3 N BKG2F 4 N BKG2F 5 N
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Group BKG3 (2 mg/kg/day): IQB-9302 Plasma Concentrationsin Female Beagle Dogs
Day 1
Collection Interval Animal Number Concentration (ng/mL)
Predose BKG3F 1 N BKG3F 2 N BKG3F 3 N BKG3F 4 N BKG3F 5 N
5 min BKG3F 1 1649 BKG3F 2 3327 BKG3F 3 1397 BKG3F 4 1192 BKG3F 5 2306
15 min BKG3F 1 1139 BKG3F 2 1814 BKG3F 3 1153 BKG3F 4 975 BKG3F 5 1603
30 min BKG3F 1 738 BKG3F 2 903 BKG3F 3 832 BKG3F 4 702 BKG3F 5 960
1 hour BKG3F 1 244 BKG3F 2 280 BKG3F 3 218 BKG3F 4 301 BKG3F 5 285
1.5 hour BKG3F 1 107 BKG3F 2 84.2 BKG3F 3 94.2 BKG3F 4 129 BKG3F 5 97.8
3 hour BKG3F 1 N BKG3F 2 N BKG3F 3 N BKG3F 4 N BKG3F 5 N
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Group BKG4 (3 mg/kg/day): IQB-9302 Plasma Concentrationsin Female Beagle Dogs
Day 1
Collection Interval Animal Number Concentration (ng/mL)
Predose BKG4F 1 N BKG4F 2 N BKG4F 3 N BKG4F 4 N BKG4F 5 N
5 min BKG4F 1 2760 BKG4F 2 2429 BKG4F 3 2271 BKG4F 4 2313 BKG4F 5 1724
15 min BKG4F 1 2247 BKG4F 2 1914 BKG4F 3 2351 BKG4F 4 1671 BKG4F 5 1117
30 min BKG4F 1 1288 BKG4F 2 1300 BKG4F 3 1274 BKG4F 4 1101 BKG4F 5 864
1 hour BKG4F 1 475 BKG4F 2 464 BKG4F 3 837 BKG4F 4 437 BKG4F 5 523
1.5 hour BKG4F 1 133 BKG4F 2 242 BKG4F 3 430 BKG4F 4 120 BKG4F 5 296
3 hour BKG4F 1 N BKG4F 2 N BKG4F 3 64.7 BKG4F 4 N BKG4F 5 54.1
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Group BKG2 (1 mg/kg/day): IQB-9302 Plasma Concentrationsin Male Beagle Dogs
Day 28
Collection Interval Animal Number Concentration (ng/mL)
Predose BKG2M 1 N BKG2M 2 N BKG2M 3 N BKG2M 4 N BKG2M 5 N
5 min BKG2M 1 1480 BKG2M 2 1851 BKG2M 3 879 BKG2M 4 1319 BKG2M 5 1930
15 min BKG2M 1 699 BKG2M 2 918 BKG2M 3 584 BKG2M 4 757 BKG2M 5 1225
30 min BKG2M 1 329 BKG2M 2 428 BKG2M 3 396 BKG2M 4 443 BKG2M 5 585
1 hour BKG2M 1 147 BKG2M 2 164 BKG2M 3 145 BKG2M 4 178 BKG2M 5 172
1.5 hour BKG2M 1 61.3 BKG2M 2 B BKG2M 3 58.4 BKG2M 4 54.6 BKG2M 5 54.7
3 hour BKG2M 1 N BKG2M 2 N BKG2M 3 N BKG2M 4 N BKG2M 5 N
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Group BKG3 (2 mg/kg/day): IQB-9302 Plasma Concentrationsin Male Beagle Dogs
Day 28
Collection Interval Animal Number Concentration (ng/mL)
Predose BKG3M 1 N BKG3M 2 N BKG3M 3 N BKG3M 4 N BKG3M 5 N
5 min BKG3M 1 2364 BKG3M 2 1187 BKG3M 3 1922 BKG3M 4 1851 BKG3M 5 1928
15 min BKG3M 1 1689 BKG3M 2 911 BKG3M 3 1255 BKG3M 4 1266 BKG3M 5 1425
30 min BKG3M 1 1067 BKG3M 2 689 BKG3M 3 792 BKG3M 4 896 BKG3M 5 742
1 hour BKG3M 1 454 BKG3M 2 319 BKG3M 3 178 BKG3M 4 279 BKG3M 5 290
1.5 hour BKG3M 1 310 BKG3M 2 124 BKG3M 3 63.4 BKG3M 4 81.3 BKG3M 5 120
3 hour BKG3M 1 53.2 BKG3M 2 N BKG3M 3 N BKG3M 4 N BKG3M 5 N
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Group BKG4 (3 mg/kg/day): IQB-9302 Plasma Concentrationsin Male Beagle Dogs
Day 28
Collection Interval Animal Number Concentration (ng/mL)
Predose BKG4M 1 N BKG4M 2 N BKG4M 3 N BKG4M 4 N BKG4M 5 N
5 min BKG4M 1 3383 BKG4M 2 2467 BKG4M 3 2929 BKG4M 4 2195 BKG4M 5 2034
15 min BKG4M 1 2469 BKG4M 2 2005 BKG4M 3 1901 BKG4M 4 1516 BKG4M 5 1452
30 min BKG4M 1 1437 BKG4M 2 1237 BKG4M 3 1575 BKG4M 4 1101 BKG4M 5 1095
1 hour BKG4M 1 512 BKG4M 2 498 BKG4M 3 665 BKG4M 4 542 BKG4M 5 594
1.5 hour BKG4M 1 176 BKG4M 2 211 BKG4M 3 438 BKG4M 4 261 BKG4M 5 320
3 hour BKG4M 1 N BKG4M 2 N BKG4M 3 N BKG4M 4 N BKG4M 5 50.8
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Group BKG2 (1 mg/kg/day): IQB-9302 Plasma Concentrationsin Female Beagle Dogs
Day 28
Collection Interval Animal Number Concentration (ng/mL)
Predose BKG2F 1 N BKG2F 2 N BKG2F 3 N BKG2F 4 N BKG2F 5 N
5 min BKG2F 1 1280 BKG2F 2 1188 BKG2F 3 1179 BKG2F 4 1507 BKG2F 5 1607
15 min BKG2F 1 589 BKG2F 2 613 BKG2F 3 857 BKG2F 4 708 BKG2F 5 958
30 min BKG2F 1 296 BKG2F 2 226 BKG2F 3 441 BKG2F 4 290 BKG2F 5 421
1 hour BKG2F 1 102 BKG2F 2 79.5 BKG2F 3 140 BKG2F 4 103 BKG2F 5 157
1.5 hour BKG2F 1 N BKG2F 2 N BKG2F 3 61.6 BKG2F 4 N BKG2F 5 B
3 hour BKG2F 1 N BKG2F 2 N BKG2F 3 N BKG2F 4 N BKG2F 5 N
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Group BKG3 (2 mg/kg/day): IQB-9302 Plasma Concentrationsin Female Beagle Dogs
Day 28
Collection Interval Animal Number Concentration (ng/mL)
Predose BKG3F 1 N BKG3F 2 N BKG3F 3 N BKG3F 4 N BKG3F 5 N
5 min BKG3F 1 1453 BKG3F 2 2866 BKG3F 3 1211 BKG3F 4 1218 BKG3F 5 2136
15 min BKG3F 1 963 BKG3F 2 1963 BKG3F 3 976 BKG3F 4 939 BKG3F 5 1534
30 min BKG3F 1 582 BKG3F 2 1131 BKG3F 3 581 BKG3F 4 564 BKG3F 5 772
1 hour BKG3F 1 152 BKG3F 2 371 BKG3F 3 249 BKG3F 4 284 BKG3F 5 283
1.5 hour BKG3F 1 67.6 BKG3F 2 205 BKG3F 3 126 BKG3F 4 123 BKG3F 5 112
3 hour BKG3F 1 N BKG3F 2 N BKG3F 3 N BKG3F 4 N BKG3F 5 N
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Group BKG4 (3 mg/kg/day): IQB-9302 Plasma Concentrationsin Female Beagle Dogs
Day 28
Collection Interval Animal Number Concentration (ng/mL)
Predose BKG4F 1 N BKG4F 2 N BKG4F 3 N BKG4F 4 N BKG4F 5 N
5 min BKG4F 1 2401 BKG4F 2 2253 BKG4F 3 2243 BKG4F 4 2243 BKG4F 5 1531
15 min BKG4F 1 1861 BKG4F 2 1556 BKG4F 3 1701 BKG4F 4 1745 BKG4F 5 1081
30 min BKG4F 1 1263 BKG4F 2 1301 BKG4F 3 1253 BKG4F 4 1144 BKG4F 5 939
1 hour BKG4F 1 392 BKG4F 2 690 BKG4F 3 628 BKG4F 4 524 BKG4F 5 565
1.5 hour BKG4F 1 162 BKG4F 2 348 BKG4F 3 419 BKG4F 4 223 BKG4F 5 330
3 hour BKG4F 1 N BKG4F 2 59.5 BKG4F 3 101 BKG4F 4 N BKG4F 5 51.1