Pharmacokinetics and tolerability of artesunate and amodiaquine alone and in combination in healthy volunteers.

European Journal of Clinical Pharmacology
Catherine OrrellKaren I Barnes

Abstract

The WHO recommends artemisinin-based combination therapies for treatment of uncomplicated falciparum malaria. At least 15 African countries have adopted artesunate plus amodiaquine as treatment policy. As no pharmacokinetic data on this combination have been published to date, we investigated its pharmacokinetic interactions and tolerability in healthy volunteers in Africa. In a randomized, three-phase, cross-over study, amodiaquine (10 mg/kg) and artesunate (4 mg/kg) were given as single oral doses to 15 healthy volunteers. Artesunate was given to all volunteers on day 0. On day 7 they received either amodiaquine or amodiaquine plus artesunate and the alternative regimen on day 28. The pharmacokinetics of artesunate and amodiaquine and their main active metabolites dihydroartemisinin and desethylamodiaquine were compared following monotherapy and combination therapy using analysis of variance. Thirteen volunteers completed the study, and pharmacokinetic parameters could be determined for twelve volunteers. When given in combination, the mean AUC was lower for dihydroartemisinin [ratio 67% (95% CI 51-88%); P = 0.008] and desethylamodiaquine [ratio 65% (95% CI 46-90%); P = 0.015] when compared with monotherapy. Adverse events of...Continue Reading

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Citations

Jan 17, 2014·Journal of Parasitic Diseases : Official Organ of the Indian Society for Parasitology·A RajanS Chandel
Feb 9, 2011·Proceedings of the National Academy of Sciences of the United States of America·Susan A CharmanJonathan L Vennerstrom
Jun 29, 2011·Antimicrobial Agents and Chemotherapy·Marcus J RijkenFrançois Nosten
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Jan 8, 2020·Antimicrobial Agents and Chemotherapy·Chu Xuan AnhMichael D Edstein
Nov 1, 2008·Personalized Medicine·Pedro Eduardo FerreiraJosé Pedro Gil
Apr 5, 2020·Pharmaceuticals·Martin D Bleasel, Gregory M Peterson
Dec 29, 2019·Scientific Reports·Lisa Evans DeWaldLisa E Hensley
Nov 16, 2019·European Journal of Pharmacology·Michał AntoszczakAdam Huczyński

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