dc.contributor.author | Byakika-Tusiime, Jayne | |
dc.contributor.author | Chinn, Leslie W. | |
dc.contributor.author | Oyugi, Jessica H. | |
dc.contributor.author | Obua, Celestino | |
dc.contributor.author | Bangsberg, David R. | |
dc.contributor.author | Kroetz, Deanna L. | |
dc.date.accessioned | 2013-02-14T14:35:39Z | |
dc.date.available | 2013-02-14T14:35:39Z | |
dc.date.issued | 2008-12-19 | |
dc.identifier.citation | Byakika-Tusiime, J., Chinn, L.W., Oyugi, J.H., Obua, C., Bangsberg, D.R., Kroetz, D.L. (2008) Steady state bioequivalence of generic and innovator formulations of stavudine, lamivudine, and nevirapine in HIV-infected Ugandan adults. PLoS ONE 3(12) | en_US |
dc.identifier.issn | 1932-6203 | |
dc.identifier.uri | http://hdl.handle.net/10570/1061 | |
dc.description | open access journal | en_US |
dc.description.abstract | Background: Generic antiretroviral therapy is the mainstay of HIV treatment in resource-limited settings, yet there is little evidence confirming the bioequivalence of generic and brand name formulations. We compared the steady-state pharmacokinetics of lamivudine, stavudine and nevirapine in HIV-infected subjects who were receiving a generic formulation (TriomuneH) or the corresponding brand formulations (EpivirH, ZeritH, and ViramuneH). Methodology/Principal Findings: An open-label, randomized, crossover study was carried out in 18 HIV-infected Ugandan subjects stabilized on Triomune-40. Subjects received lamivudine (150 mg), stavudine (40 mg), and nevirapine (200 mg) in either the generic or brand formulation twice a day for 30 days, before switching to the other formulation. At the end of each treatment period, blood samples were collected over 12 h for pharmacokinetic analysis. The main outcome measures were the mean AUC0–12h and Cmax. Bioequivalence was defined as a geometric mean ratio between the generic and brand name within the 90% confidence interval of 0.8–1.25. The geometric mean ratios and the 90% confidence intervals were: stavudine Cmax, 1.3 (0.99–1.71) and AUC0–12h, 1.1 (0.87–1.38); lamivudine Cmax, 0.8 (0.63–0.98) and AUC0–12h, 0.8 (0.65–0.99); and nevirapine Cmax, 1.1 (0.95–1.23) and AUC0–12h, 1.1 (0.95–1.31). The generic formulation was not statistically bioequivalent to the brand formulations during steady state, although exposures were comparable. A mixed random effects model identified about 50% intersubject variability in the pharmacokinetic parameters. Conclusions/Significant Findings: These findings provide support for the use of Triomune in resource-limited settings, although identification of the sources of intersubject variability in these populations is critical. | en_US |
dc.language.iso | en | en_US |
dc.publisher | Public Library of Science | en_US |
dc.subject | Bioequivalence | en_US |
dc.subject | Lamivudine | en_US |
dc.subject | Nevirapine | en_US |
dc.subject | Stavudine | en_US |
dc.subject | Generic drugs | en_US |
dc.subject | Antiretroviral therapy | en_US |
dc.subject | HIV/AIDS | en_US |
dc.subject | Uganda | en_US |
dc.title | Steady state bioequivalence of generic and innovator formulations of stavudine, lamivudine, and nevirapine in HIV-infected Ugandan adults | en_US |
dc.type | Journal article, peer reviewed | en_US |