TY - JOUR
T1 - Nevirapine-based antiretroviral therapy impacts artesunate and dihydroartemisinin disposition in HIV-infected Nigerian adults
AU - Fehintola, Fatai A.
AU - Scarsi, Kimberly K.
AU - Ma, Qing
AU - Parikh, Sunil
AU - Morse, Gene D.
AU - Taiwo, Babafemi
AU - Akinola, Ibrahim Tope
AU - Adewole, Isaac F.
AU - Lindegardh, Niklas
AU - Phakderaj, Aphiradee
AU - Ojengbede, Oladosu
AU - Murphy, Robert L.
AU - Akinyinka, Olusegun O.
AU - Aweeka, Francesca T.
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
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U2 - 10.1155/2012/703604
DO - 10.1155/2012/703604
M3 - Article
C2 - 22500218
AN - SCOPUS:84873831726
SN - 2090-1240
VL - 2012
JO - AIDS Research and Treatment
JF - AIDS Research and Treatment
M1 - 703604
ER -