Concomitant nevirapine impacts pharmacokinetic exposure to the antimalarial artemether-lumefantrine in African children

作者：Liusheng Huang, Vincent J. Carey, Jane C. Lindsey, Florence Marzan, David Gingrich, Bobbie Graham, Linda Barlow‐Mosha, Phionah Kibalama Ssemambo, Portia Kamthunzi, Sharon Nachman, Sunil Parikh, Francesca Aweeka, the IMPAACT P1079 protocol team · 发表于：PLoS ONE · 年份：2017 · DOI：10.1371/journal.pone.0186589 · 被引用次数：9 · 研究领域：Malaria Research and Control、HIV/AIDS drug development and treatment、Pharmaceutical Quality and Counterfeiting

BACKGROUND: The antiretroviral drug nevirapine and the antimalarial artemisinin-based combination therapy artemether-lumefantrine are commonly co-administered to treat malaria in the context of HIV. Nevirapine is a known inhibitor of cytochrome P450 3A4, which metabolizes artemether and lumefantrine. To address the concern that the antiretroviral nevirapine impacts the antimalarial artemether-lumefantrine pharmacokinetics, a prospective non-randomized controlled study in children presenting with uncomplicated malaria and HIV in sub-Saharan Africa was carried out. METHODS: Participants received artemether-lumefantrine (20/120 mg weight-based BID) for 3 days during nevirapine-based antiretroviral therapy (ART) co-administration (158-266 mg/m2 QD). HIV positive participants who were not yet on ART drugs were also enrolled as the control group. The target enrollment was children aged 3-12 years (n = 24 in each group). Intensive pharmacokinetics after the last artemether-lumefantrine dose was assessed for artemether, its active metabolite dihydroartemisinin, and lumefantrine. Pharmacokinetic parameters (area under the plasma concentration vs. time curve (AUC), maximum concentration and day 7 lumefantrine concentrations) were estimated using non-compartmental methods and compared to controls. RESULTS: Nineteen children (16 on nevirapine and three not on ART) enrolled. Fifteen of the 16 (aged 4 to 11 years) on nevirapine-based ART were included in the pharmacokinetic analysis. Due t...