Evaluation of the bioequivalence of zidovudine 100 mg capsules in healthy Thai male volunteers.
OBJECTIVE
The bioequivalence study of two oral formulations of zidovudine were evaluated; Antivir (Government Pharmaceutical Organization (GPO), Thailand) as the test formulation and Retrovir (Glaxo-SmithKline, USA), as the reference formulation.


METHODS
The two products were orally administered as a single dose of 100 mg zidovudine three capsules according to a randomized two-way crossover design to 28 healthy fasted Thai male volunteers. The washout period between treatments was 1 week. After drug administration, serial blood samples were collected at a specific time interval from 0-10 hours. The plasma zidovudine concentrations were determined via HPLC technique. Individual plasma zidovudine concentration-time profile was analyzed for relevant pharmacokinetic parameters; the comparative bioavailability of the two products was determined by the analysis of variance (ANOVA) for two way crossover design, using logarithmic transformed data.


RESULTS
The results found that the mean peak (X+/- SD) plasma concentration (Cmax) of Antivir was 3.34 +/- 0.15 ng/mL and of Retrovir was 3.32 +/- 0.21 ng/mL. The 90% confidence interval (CI) for the difference of mean Cmax was 90.76-120.81%. The time to peak plasma concentration (Tmax) of Antivir was 0.49 +/- 0.16 hours and for Retrovir was 0.62 +/- 0.35 hours with a difference time to peak of 20.96%. The half life (t1/2) of Antivir was 1.16 +/- 0.28 hours and t1/2 of Retrovir was 1.05 +/- 0.25 hours. The mean area under the curve (AUC0-->t) of Antivir was 3.34 +/- 0.12 ng.hr/mL and of Retrovir was 3.35 +/- 0.15 ng.hr/mL. The 90%CI for the difference ofmean AUC0-->t was 91.83-103.99%. The mean AUC0-->infinity of Antivir was 3.37 +/- 0.12 nghr/mL and for and Retrovir was 3.38 +/- 0.14 ng.hr/mL. The 90%CI for the difference of mean AUC0-->infinity was 91.22-104.69%.


CONCLUSIONS
The present study revealed that the 90%CI for the difference of Cmax AUC0-->t and AUC0-->infinity means were in the criteria ofacceptance, which should be within 80-125%. Thus, the present study demonstrated the bioequivalence of the test drug (Antivir) and the reference drug (Retrovir).
Chompootaweep
Sumana
S
Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
Poonsrisawat
Jitisak
J
Xumseang
Pratoommal
P
D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002214:Capsules; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D013785:Thailand; D013810:Therapeutic Equivalency; D015215:Zidovudine / Q000008:administration & dosage / Q000493:pharmacokinetics*
D019380:Anti-HIV Agents; D002214:Capsules; D015215:Zidovudine