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AIDS Res Treat. 2012;2012:703604. doi: 10.1155/2012/703604. Epub 2012 Mar 5.

Nevirapine-Based Antiretroviral Therapy Impacts Artesunate and Dihydroartemisinin Disposition in HIV-Infected Nigerian Adults.

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1
Department of Clinical Pharmacology, University College Hospital and Department of Pharmacology & Therapeutics, College of Medicine, University of Ibadan, Ibadan, Nigeria.

Abstract

BACKGROUND:

Nevirapine- (NVP-) based antiretroviral therapy (ART) and artesunate-amodiaquine are frequently coprescribed in areas of HIV and malaria endemicity. We explored the impact of this practice on artesunate and dihydroartemisinin pharmacokinetics.

METHODS:

We conducted a parallel-group pharmacokinetic comparison between HIV-infected patients receiving NVP-based ART (n = 10) and ART-naive controls (n = 11). Artesunate-amodiaquine 200/600 mg was given daily for three days. Measurement of drug concentrations occurred between 0 and 96 hours after the final dose. Pharmacokinetic parameters were determined using noncompartmental analysis.

RESULTS:

Comparing the NVP group to controls, clearance of artesunate was reduced 50% (1950 versus 2995 L/h; P = 0.03), resulting in a 45% increase in the AUC(0-96) (105 versus 69 ug(∗)hr/L; P = 0.02). The half-life of dihydroartemisinin was shorter in the NVP group (1.6 versuss 3.2 h; P = 0.004), but other dihydroartemisinin pharmacokinetic parameters were unchanged. A lower conversion of artesunate to dihydroartemisinin was observed in the NVP group (dihydroartemisinin: artesunate AUC(0-96) = 5.6 versuss 8.5 in NVP and control groups, respectively, P = 0.008).

CONCLUSION:

Although NVP-containing ART impacted some pharmacokinetic parameters of artesunate and dihydroartemisinin, overall exposure was similar or better in the NVP group.

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