1. Pharmacokinetics of Antiretroviral Drug Varies With Formulation in the Target Population of Children With HIV-1.
- Author
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Kasirye, P, Kendall, L, Adkison, K K, Tumusiime, C, Ssenyonga, M, Bakeera-Kitaka, S, Nahirya-Ntege, P, Mhute, T, Kekitiinwa, A, Snowden, W, Burger, D M, Gibb, D M, and Walker, A S
- Subjects
PHARMACOKINETICS ,ANTIRETROVIRAL agents ,HIV-positive persons ,JUVENILE diseases ,AZIDOTHYMIDINE ,ABACAVIR ,LAMIVUDINE - Abstract
The bioequivalence of formulations is usually evaluated in healthy adult volunteers. In our study in 19 HIV-1-infected Ugandan children (1.8-4 years of age, weight 12 to <15 kg) receiving zidovudine, lamivudine, and abacavir solutions twice a day for ≥24 weeks, the use of scored tablets allowed comparison of plasma pharmacokinetics of oral solutions vs. tablets. Samples were collected 0, 1, 2, 4, 6, 8, and 12 h after each child's last morning dose of oral solution before changing to scored tablets of Combivir (coformulated zidovudine + lamivudine) and abacavir; this was repeated 4 weeks later. Dose-normalized area under curve (AUC)
0-12 and peak concentration (Cmax ) for the tablet formulation were bioequivalent with those of the oral solution with respect to zidovudine and abacavir (e.g., dose-normalized geometric mean ratio (dnGMR) (tablet:solution) for zidovudine and abacavir AUC0-12 were 1.01 (90% confidence interval (CI) 0.87-1.18) and 0.96 (0.83-1.12), respectively). However, lamivudine exposure was ~55% higher with the tablet formulation (AUC0-12 dnGMR = 1.58 (1.37-1.81), Cmax dnGMR = 1.55 (1.33-1.81)). Although the clinical relevance of this finding is unclear, it highlights the impact of the formulation and the importance of conducting bioequivalence studies in target pediatric populations. [ABSTRACT FROM AUTHOR]- Published
- 2012
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