Single dose pharmacokinetics of oral artemether in healthy Malaysian volunteers

Abstract

Aims To determine the pharmacokinetics of artemether (ARM) and its principal active metabolite, dihydroartemisinin (DHA) in healthy volunteers.

Methods Six healthy male Malaysian subjects were given a single oral dose of 200 mg artemether. Blood samples were collected to 72 h. Plasma concentrations of the two compounds were measured simultaneously by reversed-phase h.p.l.c. with electrochemical detection in the reductive mode.

Results Mean (± s.d.) maximum concentrations of ARM, 310±153 μg l⁻¹, were reached 1.88±0.21 h after drug intake. The mean elimination half-life was 2.00±0.59 h, and the mean AUC 671±271 μg l⁻¹ h. The mean C_max of DHA, 273±64 μg l⁻¹, was observed at 1.92±0.13 h. The mean AUC of DHA was 753±233 μg h l⁻¹. ARM and DHA were stable at ≤−20° C for at least 4 months in plasma samples.

Conclusions The relatively short half-life of ARM may be one of the factors responsible for the poor radical cure rate of falciparum malaria with regimens employing daily dosing. In view of the rapid loss of DHA in plasma samples held at room temperature (26° C) it is recommended to store them at a temperature of ≤−20° C as early as possible after sample collection.

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