Publication: Disposition of amodiaquine and desethylamodiaquine in HIV-infected nigerian subjects on nevirapine-containing antiretroviral therapy
Issued Date
2014-01-01
Resource Type
ISSN
14602091
03057453
03057453
Other identifier(s)
2-s2.0-84898464820
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Antimicrobial Chemotherapy. Vol.69, No.5 (2014), 1370-1376
Suggested Citation
Kimberly K. Scarsi, Fatai A. Fehintola, Qing Ma, Francesca T. Aweeka, Kristin M. Darin, Gene D. Morse, Ibrahim Temitope Akinola, Waheed A. Adedeji, Niklas Lindegardh, Joel Tarning, Oladosu Ojengbede, Isaac F. Adewole, Babafemi Taiwo, Robert L. Murphy, Olusegun O. Akinyinka, Sunil Parikh Disposition of amodiaquine and desethylamodiaquine in HIV-infected nigerian subjects on nevirapine-containing antiretroviral therapy. Journal of Antimicrobial Chemotherapy. Vol.69, No.5 (2014), 1370-1376. doi:10.1093/jac/dkt513 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/34870
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Title
Disposition of amodiaquine and desethylamodiaquine in HIV-infected nigerian subjects on nevirapine-containing antiretroviral therapy
Other Contributor(s)
Northwestern University Feinberg School of Medicine
University of Ibadan
University College Hospital, Ibadan
University at Buffalo, State University of New York
University of California, San Francisco
Mahidol University
Nuffield Department of Clinical Medicine
Yale University
University of Nebraska Medical Center
University of Ibadan
University College Hospital, Ibadan
University at Buffalo, State University of New York
University of California, San Francisco
Mahidol University
Nuffield Department of Clinical Medicine
Yale University
University of Nebraska Medical Center
Abstract
Objectives: Artesunate plus amodiaquine is used for malaria treatment in regions with overlapping HIV endemicity. Co-administration of artesunate/amodiaquine with antiretroviral therapy (ART) may result in drug-drug interactions, but minimal data exist. This study evaluated the impact of nevirapine-based ART, containing a backbone of zidovudine and lamivudine, on the disposition of amodiaquine and its active metabolite, desethylamodiaquine (DEAQ). Methods: This was an open-label, parallel-group pharmacokinetic comparison between HIV-infected, adult subjects receiving steady-state nevirapine-based ART (n1/410) and ART-naive subjects (control group, n1/411). All subjects received a loose formulation of artesunate/amodiaquine (200/600 mg) daily for 3 days, with serial pharmacokinetic sampling over 96 h following the final dose of artesunate/amodiaquine. Amodiaquine and DEAQ were quantified using a validated HPLC method with UV detection. Pharmacokinetic parameters were determined using standard non-compartmental methods. Results: Exposures to both amodiaquine and DEAQ were significantly lower in the nevirapine-based ART group compared with the control group (amodiaquine AUC0-24 145 versus 204 ng.h/mL, P1/40.02; DEAQ AUC0-96 14571 versus 21648 ng.h/mL, P<0.01). The AUCDEAQ/AUCamodiaquine ratio was not different between groups (ART group 116 versus control group 102, P1/40.67). Conclusions: Subjects on nevirapine-based ART had lower exposure to both amodiaquine and DEAQ (28.9% and 32.7%, respectively). Consequently, this may negatively impact the effectiveness of artesunate/amodiaquine in HIV-infected individuals on this ART combination. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.