title: Nevirapine-Based Antiretroviral Therapy Impacts Artesunate and Dihydroartemisinin Disposition in HIV-Infected Nigerian Adults.
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.
authors.affiliation: Department of Clinical Pharmacology, University College Hospital and Department of Pharmacology & Therapeutics, College of Medicine, University of Ibadan, Ibadan, Nigeria.
authors.forename: Fatai A
authors.initials: FA
authors.lastname: Fehintola
authors.forename: Kimberly K
authors.initials: KK
authors.lastname: Scarsi
authors.forename: Qing
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authors.lastname: Ma
authors.forename: Sunil
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authors.lastname: Parikh
authors.forename: Gene D
authors.initials: GD
authors.lastname: Morse
authors.forename: Babafemi
authors.initials: B
authors.lastname: Taiwo
authors.forename: Ibrahim Tope
authors.initials: IT
authors.lastname: Akinola
authors.forename: Isaac F
authors.initials: IF
authors.lastname: Adewole
authors.forename: Niklas
authors.initials: N
authors.lastname: Lindegardh
authors.forename: Aphiradee
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authors.lastname: Phakderaj
authors.forename: Oladosu
authors.initials: O
authors.lastname: Ojengbede
authors.forename: Robert L
authors.initials: RL
authors.lastname: Murphy
authors.forename: Olusegun O
authors.initials: OO
authors.lastname: Akinyinka
authors.forename: Francesca T
authors.initials: FT
authors.lastname: Aweeka