Plasma concentrations of artemether and its major plasma metabolite, dihydroartemisinin, following a 5-day regimen of oral artemether, in patients with uncomplicated falciparum malaria

Abstract

Plasma concentrations of artemether and its active plasma metabolite (dihydroartemisinin) were measured in 49 male, Thai patients with acute, uncomplicated, multidrug-resistant, Plasmodium falciparum malaria, following their treatment with oral artemether (300 mg on the first day, then 100 mg daily for another 4 days). Four patients recrudesced (on days 19-22). After the first dose, artemether became undetectable in ≤ 18 h and this drug was also undetectable in samples collected immediately before each dose. Although dihydroartemisinin followed similar trends, three patients had detectable plasma concentrations of this metabolite 24 h after the first dose (i.e. immediately before the second dose). Median (range) values for plasma concentrations of dihydroartemisinin 6 h [354 (150-751)) v. 196 (178-220) ng/ml] and 12 h [158 (25-420) v. 54 (25-115) ng/ml] after the initial dose, estimated antimalarial activities (calculated as dihydroartemisinin equivalents) 6 h [331 (78.2-644.1) v. 23 (183.3-270) nmol/litre] and 12 h [98.3 (10-192.2) v. 56.7 (9.8-59.4) nmol/litre] after the initial dose, and the corresponding 'areas under the curves' (AUC) [3684 (1562-8216) v. 834 (1401-2030) ng.h/ml] were all significantly higher in the patients with sensitive responses than in those who recrudesced.