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 4×80 mg artemether orally ( n=48) or 4×80–480 mg co-artemether ( n=40), a combination of artemether and lumefantrine (benflumetol). Lag 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 paralleled artemether pharmacokinetics. Artemether C max after the last dose was one-third of the C max after the first dose while, inversely, dihydroartemisinin C max 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.