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 approximately 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.
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.; Walker, A.S. Pharmacokinetics of Antiretroviral Drug Varies With Formulation in the Target Population of Children With HIV-1. Clinical Pharmacology and Therapeutics (2012) 91 (2) 272-280. [DOI: 10.1038/clpt.2011.225]