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

Autor: Fatai A. Fehintola, Kimberly K. Scarsi, Qing Ma, Sunil Parikh, Gene D. Morse, Babafemi Taiwo, Ibrahim Tope Akinola, Isaac F. Adewole, Niklas Lindegardh, Aphiradee Phakderaj, Oladosu Ojengbede, Robert L. Murphy, Olusegun O. Akinyinka, Francesca T. Aweeka
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Zdroj: AIDS Research and Treatment, Vol 2012 (2012)
Druh dokumentu: article
ISSN: 2090-1240
2090-1259
DOI: 10.1155/2012/703604
Popis: 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 AUC0-96 (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 AUC0-96=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.
Databáze: Directory of Open Access Journals
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