Bioequivalence and pharmacokinetics of two zidovudine formulations in healthy Brazilian volunteers: an open-label, randomized, single-dose, two-way crossover study.
BACKGROUND
Zidovudine is a thymidine nucleoside reverse transcriptase inhibitor with activity against HIV type 1. Some (approximately 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-infinity), 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-infinity) 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(max)0-t, and AUC(0-infinity) 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-infinity) 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-infinity), 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).
Dos Reis Serra
Cristina Helena
CH
Departamento de Farmácia, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, Brazil. chserra@usp.br
Mori Koono
Eunice Emiko
EE
Kano
Eunice Kazue
EK
Schramm
Simone Grigoleto
SG
Armando
Yara Popst
YP
Porta
Valentina
V
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency; D015215:Zidovudine / Q000008:administration & dosage / Q000493:pharmacokinetics*
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine