PLASMA-CONCENTRATIONS OF ARTEMETHER AND ITS MAJOR PLASMA METABOLITE, DIHYDROARTEMISININ, FOLLOWING A 5-DAY REGIMEN OF ORAL ARTEMETHER, IN PATIENTS WITH UNCOMPLICATED FALCIPARUM-MALARIA

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, f ollowing 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 less than or equal to 18 h and this drug was also undetectable in samp les collected immediately before each dose. Although dihydroartemisini n followed similar trends, three patients had detectable plasma concen trations of this metabolite 24 h after the first dose (i.e. immediatel y before the second dose). Median (range) values for plasma concentrat ions 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, e stimated antimalarial activities (calculated as dihydroartemisinin equ ivalents) 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 dos e, and the corresponding 'areas under the curves' (AUG) [3684 (1562-82 16) v. 834 (1401-2030) ng.h/ml] were all significantly higher in the p atients with sensitive responses than in those who recrudesced.