RESUMEN
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. MATERIAL AND METHOD: 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%. CONCLUSION: 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).