Disposition of amodiaquine and desethylamodiaquine in HIV-infected Nigerian subjects on nevirapine-containing antiretroviral therapy.
Article Details
- CitationCopy to clipboard
Scarsi KK, Fehintola FA, Ma Q, Aweeka FT, Darin KM, Morse GD, Akinola IT, Adedeji WA, Lindegardh N, Tarning J, Ojengbede O, Adewole IF, Taiwo B, Murphy RL, Akinyinka OO, Parikh S
Disposition of amodiaquine and desethylamodiaquine in HIV-infected Nigerian subjects on nevirapine-containing antiretroviral therapy.
J Antimicrob Chemother. 2014 May;69(5):1370-6. doi: 10.1093/jac/dkt513. Epub 2014 Jan 19.
- PubMed ID
- 24446424 [ View in PubMed]
- 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 AUC(0)(-)(2)(4) 145 versus 204 ng.h/mL, P = 0.02; DEAQ AUC(0)(-)(9)(6) 14,571 versus 21,648 ng.h/mL, P < 0.01). The AUCDEAQ/AUC(amodiaquine) 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.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Amodiaquine Cytochrome P450 1A1 Protein Humans UnknownSubstrateDetails Amodiaquine Cytochrome P450 1B1 Protein Humans UnknownSubstrateDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareAmodiaquineZidovudine Zidovudine may increase the neutropenic activities of Amodiaquine. AmodiaquineEfavirenz Efavirenz may increase the hepatotoxic activities of Amodiaquine.