Multiple dose pharmacokinetics of artemether in Chinese patients with uncomplicated falciparum malaria.
Multiple dose pharmacokinetics of artemether and dihydroartemisinin were investigated in chinese patients treated for malaria. They received over 2 days either 4 x 80 mg artemether orally (n = 48) or 4 x 80-480 mg co-artemether (n = 40), a combination of artemether and lumefantrine (benflumetol). Lag time = 0.48 h (mean), Cmax after first dose = 157 ng/ml, t(max) = 1.73 h and elimination half-life = 1.16 h. The lag and absorption times were 0.5 h longer for co-artemether compared with artemether. Dihydroartemisinin paralleled artemether pharmacokinetics. Artemether Cmax after the last dose was one-third of the Cmax after the first dose while, inversely, dihydroartemisinin Cmax increased over time. We suggest that auto-induction of gut mucosa enzymes and/or liver enzymes causes a time-dependent increase in first-pass metabolisation of artemether.
Department of Clinical Pharmacology and Pharmacotherapy, Academic Medical Center, Amsterdam, The Netherlands.
M A
MA
van Agtmael
S
S
Cheng-Qi
J X
JX
Qing
R
R
Mull
C J
CJ
van Boxtel
D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000077549:Artemether; D037621:Artemisinins; D002681:China; D004311:Double-Blind Method; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D005449:Fluorenes / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D000078102:Lumefantrine; D016778:Malaria, Falciparum / Q000097:blood* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D008956:Models, Chemical; D012717:Sesquiterpenes / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013997:Time Factors
D000962:Antimalarials; D037621:Artemisinins; D004983:Ethanolamines; D005449:Fluorenes; D012717:Sesquiterpenes; C039060:artenimol; D000077549:Artemether; D000078102:Lumefantrine