Bioequivalence Study of Zidovudine 100 Mg Capsule with TwoWay Crossover Design

Abstract

Zidovudine is a synthetic nucleoside analogue, specifically a nucleoside reverse transcriptase inhibitor (NRTI), that inhibits the replication of retroviruses, including HIV. Study Objective: This study objective was to determine the bioequivalence of Zidovudine 100 mg capsules produced by PT Kimia Farma Tbk compared to Retrovir 100 mg capsules produced by GlaxoSmithKline Pharmaceuticals S.A, in healthy subjects Methods: The study was conducted in a randomized, single-dose, open-label, two-way crossover design (2 treatments, 2 periods, and 2 sequences) under fasting state with 7 (seven) days washed-out period between each period. The number of subjects who participated and completed the study were 31 of 32 adult male and female. One subject dropped out from 2nd period because of personal reason. The subjects received an explanation of the study and signed informed consent. Subjects fasted for a minimum of 8 hours before receiving the test drug and reference drug. Blood samples were collected 15 times at the following time points: 0 hours (before drug administration), 0.16, 0.33, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 10 hours after drug administration. Plasma concentrations of the drug were determined by LC-MS/MS method. The pharmacokinetic parameters calculated in this study are AUC0-t, AUC0-inf, Cmax, tmax, and t½, while the statistical interval proposed was 80.00 - 125.00% for AUC0-t and Cmax with 90% Confidence Interval (CI) with α = 5.00%. Results: The main pharmacokinetic parameters of the test drug Zidovudine (BN: G2 1346 J) compared to reference drug, Retrovir (BN: JN8K) were calculated based on geometric mean ratio and 90% confidence interval (CI). The results for AUC0-t and Cmax were 101.65% (96.77- 106.83%) and 95.63% (84.09-108.76%) respectively, with intra-subject variability (%CV) for AUC0-t and Cmax were 11.49% and 30.47%. Hence, the number of 31 subjects has adequate number for required power of study. Conclusion: Based on the AUC0-t and Cmax values, Zidovudine 100 mg Capsules Produced by PT. Kimia Farma Tbk is bioequivalent to Retrovir 100 mg Capsules Produced by GlaxoSmithKline Pharmaceuticals S.A.