Nevirapine-based antiretroviral therapy impacts artesunate and dihydroartemisinin disposition in HIV-infected Nigerian adults

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

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13 Scopus citations

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(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=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.

Original languageEnglish (US)
Article number703604
JournalAIDS Research and Treatment
Volume2012
DOIs
StatePublished - Dec 1 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Dermatology
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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    Fehintola, F. A., Scarsi, K. K., Ma, Q., Parikh, S., Morse, G. D., Taiwo, B., Akinola, I. T., Adewole, I. F., Lindegardh, N., Phakderaj, A., Ojengbede, O., Murphy, R. L., Akinyinka, O. O., & Aweeka, F. T. (2012). Nevirapine-based antiretroviral therapy impacts artesunate and dihydroartemisinin disposition in HIV-infected Nigerian adults. AIDS Research and Treatment, 2012, [703604]. https://doi.org/10.1155/2012/703604