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- Title
Disposition of amodiaquine and desethylamodiaquine in HIV-infected Nigerian subjects on nevirapine-containing antiretroviral therapy.
- Authors
Scarsi, Kimberly K.; Fehintola, Fatai A.; Ma, Qing; Aweeka, Francesca T.; Darin, Kristin M.; Morse, Gene D.; Akinola, Ibrahim Temitope; Adedeji, Waheed A.; Lindegardh, Niklas; Tarning, Joel; Ojengbede, Oladosu; Adewole, Isaac F.; Taiwo, Babafemi; Murphy, Robert L.; Akinyinka, Olusegun O.; Parikh, Sunil
- 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 (n = 10) and ART-naive subjects (control group, n = 11). 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, P = 0.02; DEAQ AUC0–96 14 571 versus 21 648 ng·h/mL, P < 0.01). The AUCDEAQ/AUCamodiaquine ratio was not different between groups (ART group 116 versus control group 102, P = 0.67). 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.
- Subjects
AMODIAQUINE; MALARIA treatment; HIV-positive persons; PHARMACOKINETICS; NEVIRAPINE; THERAPEUTICS
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2014, Vol 69, Issue 5, p1370
- ISSN
0305-7453
- Publication type
Article
- DOI
10.1093/jac/dkt513