Bioequivalence and pharmacokinetics of two zidovudine formulations in healthy brazilian volunteers: An open-label, randomized, single-dose, two-way crossover study

Abstract

Background: Zidovudine is a thymidine nucleoside reverse transcriptase inhibitor with activity against HIV type 1. Some (~8) generic formulations of zidovudine are available in Brazil; however, based on a literature search, information concerning their bioavailability and pharmacokinetic properties in the Brazilian population has not been reported. Objective: The aim of this study was to compare the bioavailability and pharmacokinetic properties of 2 capsule formulations of zidovudine 100 mg in healthy Brazilian volunteers. Methods: This open-label, randomized, 2-way crossover study utilized a 1-week washout period between doses. Blood samples were collected for 8 hours after a single dose of zidovudine 100-mg test (Zidovudina, Fundação para o Remédio Popular, São Paulo, Brazil) or reference formulation (Retrovir®, GlaxoSmithKline,Philadelphia,Pennsylvania).Plasma zidovudine concentrations were determined using a validated high-performance liquid chromatography method with ultraviolet detection at 265 nm. C max, T max, AUC 0-t, AUC 0-∞, t 1/2, and the elimination constant (k e) were determined using noncompartmental analysis. The formulations were considered bioequivalent if the 90% CIs for C max, AUC 0-t, and AUC 0-∞ fell within the interval of 80% to 125%,the regulatory definition set by the US Food and Drug Administration (FDA). Results: Twenty-four healthy volunteers (12 males, 12 females; mean age, 27 years; weight, 60 kg; height, 167 cm) were enrolled and completed the study. The 90% CIs of the treatment ratios for the logarithmic transformed values of C max, AUC max0-t, and AUC 0-∞ were 80.0% to 113.6%, 93.9% to 109.7%, and 93.6% to 110.1%, respectively. The values for the test and reference formulations were within the FDA bioequivalence definition intervals of 80% to 125%. Conclusions: In this small study in healthy subjects, no statistically significant differences in C max, AUC 0-t, and AUC 0-∞ were found between the test and reference formulations of zidovudine 100-mg capsules. The 90% CIs for the mean ratio values for the test and reference formulations of AUC 0-t, AUC 0-∞, and C max indicated that the reported data were entirely within the bioequivalence acceptance range proposed by the FDA of 80% to 125% (using log-transformed data).