Disposition of amodiaquine and desethylamodiaquine in HIV-infected Nigerian subjects on nevirapine-containing antiretroviral therapy

作者：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

来源：Journal of Antimicrobial Chemotherapy, 2014, 69(5): 1370-1376.

DOI：10.1093/jac/dkt513

• drug-drug interactions
• pharmacokinetics
• antimalarial

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 drugdrug 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). %26lt;br%26gt;This was an open-label, parallel-group pharmacokinetic comparison between HIV-infected, adult subjects receiving steady-state nevirapine-based ART (n10) and ART-naive subjects (control group, n11). 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. %26lt;br%26gt;Exposures to both amodiaquine and DEAQ were significantly lower in the nevirapine-based ART group compared with the control group (amodiaquine AUC(024) 145 versus 204 ngh/mL, P0.02; DEAQ AUC(096) 14571 versus 21648 ngh/mL, P0.01). The AUC(DEAQ)/AUC(amodiaquine) ratio was not different between groups (ART group 116 versus control group 102, P0.67). %26lt;br%26gt;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.

• 出版日期2014-5
• 单位西北大学