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AIDS Res Treat. 2012; 2012: 703604.
Published online Mar 5, 2012. doi:  10.1155/2012/703604
PMCID: PMC3303559
Nevirapine-Based Antiretroviral Therapy Impacts Artesunate and Dihydroartemisinin Disposition in HIV-Infected Nigerian Adults
Fatai A. Fehintola, 1 Kimberly K. Scarsi, 2 Qing Ma, 3 Sunil Parikh, 4 Gene D. Morse, 3 Babafemi Taiwo, 2 Ibrahim Tope Akinola, 5 Isaac F. Adewole, 6 Niklas Lindegardh, 7 Aphiradee Phakderaj, 7 Oladosu Ojengbede, 6 Robert L. Murphy, 2 Olusegun O. Akinyinka, 8 * and Francesca T. Aweeka 9
1Department of Clinical Pharmacology, University College Hospital and Department of Pharmacology & Therapeutics, College of Medicine, University of Ibadan, Ibadan, Nigeria
2Division of Infectious Diseases & Center for Global Health, Northwestern University Feinberg School of Medicine, Chicago, IL 60614, USA
3Translational Pharmacology Research Core, NYS Center of Excellence in Bioinformatics and Life Sciences, Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, NY 14203, USA
4Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA 94110, USA
5Department of Obstetrics & Gynecology, University College Hospital, Ibadan, Nigeria
6Department of Obstetrics & Gynecology, College of Medicine, University of Ibadan, Ibadan, Nigeria
7Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
8Department of Pediatrics, College of Medicine, University of Ibadan, Ibadan, Nigeria
9Drug Research Unit, Department of Clinical Pharmacy, School of Pharmacy, University of California, San Francisco, San Francisco, CA 94110, USA
*Olusegun O. Akinyinka: asegun/at/hotmail.com
Academic Editor: Gary Maartens
Received October 16, 2011; Accepted December 15, 2011.
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 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.
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