title: 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 < or = 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.
authors.affiliation: Clinical Pharmacology Unit, Faculty of Tropical Medicine, Mahidol University, Pyathai, Bangkok, Thailand. tmjlt@mucc.mahidol.ac.th
authors.forename: J
authors.initials: J
authors.lastname: Karbwang
authors.forename: K
authors.initials: K
authors.lastname: Na-Bangchang
authors.forename: A
authors.initials: A
authors.lastname: Thanavibul
authors.forename: P
authors.initials: P
authors.lastname: Molunto
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000097:blood* / Q000627:therapeutic use; D000077549:Artemether; D037621:Artemisinins; D018432:Drug Resistance, Multiple; D005500:Follow-Up Studies; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D012717:Sesquiterpenes / Q000097:blood* / Q000627:therapeutic use
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; C039060:artenimol; D000077549:Artemether