title: A randomized crossover study to determine bioequivalence of generic and brand name nevirapine, zidovudine, and lamivudine in HIV-negative women in India.
abstract: Low-cost generic antiretroviral drugs are available in resource-limited settings for treatment of HIV infections. However, few bioequivalence data in specific populations in which these generics are likely to be used are available. We conducted a randomized crossover bioequivalence study of generic and brand name formulations of nevirapine, zidovudine, and lamivudine in HIV-negative Indian women using US Food and Drug Administration (FDA) criteria. Subjects took single doses of all formulations separated by a 14-day washout period. Plasma concentrations were measured over 96 hours during each study period. Average bioequivalence was determined using natural log-transformed maximum concentration (C(max)) and area-under-the-concentration-time curve (AUC) mean ratio data. Fifteen Indian women were enrolled. The 90% confidence intervals for nevirapine (14 subjects) and lamivudine (15 subjects) C(max), AUC from 0 to the last measurable time point (AUC(0-t)), and AUC from 0 to infinity (AUC(0-infinity)) mean ratios and zidovudine (15 subjects) AUC(0-t) and AUC(0-infinity) mean ratios were all within 0.80 to 1.25. However, the 90% confidence interval for zidovudine C(max) mean ratio was 0.70 to 1.46. Generic and brand name nevirapine and lamivudine met FDA average bioequivalence criteria. Lack of average bioequivalence for zidovudine was found for C(max) but is not expected to be clinically significant, because the total AUC values were similar between formulations.
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA. wynnx004@umn.edu
authors.forename: Heather E
authors.initials: HE
authors.lastname: Vezina
authors.forename: Keith
authors.initials: K
authors.lastname: Henry
authors.forename: G D
authors.initials: GD
authors.lastname: Ravindran
authors.forename: Anura V
authors.initials: AV
authors.lastname: Kurpad
authors.forename: Tony D S
authors.initials: TD
authors.lastname: Raj
authors.forename: Kathy
authors.initials: K
authors.lastname: Fox
authors.forename: Dennis
authors.initials: D
authors.lastname: Weller
authors.forename: Richard C
authors.initials: RC
authors.lastname: Brundage
authors.forename: Winston
authors.initials: W
authors.lastname: Cavert
authors.forename: Henry H
authors.initials: HH
authors.lastname: Balfour
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D015331:Cohort Studies; D016001:Confidence Intervals; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D016568:Drugs, Generic / Q000493:pharmacokinetics*; D005260:Female; D015658:HIV Infections / Q000517:prevention & control / Q000635:transmission; D018023:HIV Seronegativity / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007194:India; D019259:Lamivudine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019829:Nevirapine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013607:Tablets; D013810:Therapeutic Equivalency; D015215:Zidovudine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D019380:Anti-HIV Agents; D004338:Drug Combinations; D016568:Drugs, Generic; D013607:Tablets; D019259:Lamivudine; D015215:Zidovudine; D019829:Nevirapine