Multiple dose pharmacokinetics of artemether in Chinese patients with uncomplicated falciparum malaria

Multiple dose pharmacokinetics of artemether and dihydroartemisinin were in vestigated in chinese patients treated for malaria. They received over 2 da ys either 4 x 80 mg artemether orally (n = 48) or 4 x 80-480 mg co-artemeth er (n = 40), a combination of artemether and lumefantrine (benflumetol). La g time = 0.48 h (mean), C-max 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 par alleled artemether pharmacokinetics. Artemether C-max after the last dose w as one-third of the C-max after the first dose while, inversely, dihydroart emisinin C-max increased over time. We suggest that auto-induction of gut m ucosa enzymes and/or liver enzymes causes a time-dependent increase in firs t-pass metabolisation of artemether. (C) 1999 Elsevier Science B.V. and Int ernational Society of Chemotherapy. All rights reserved.