SINGLE-DOSE PHARMACOKINETICS OF ORAL ARTEMETHER IN HEALTHY MALAYSIAN VOLUNTEERS

Aims To determine the pharmacokinetics of artemether (ARM) and its pri ncipal active metabolite, dihydroartemisinin (DHA) in healthy voluntee rs. Methods Six healthy male Malaysian subjects were given a single or al dose of 200 mg artemether. Blood samples were collected to 72 h. Pl asma concentrations of the two compounds were measured simultaneously by reversed-phase h.p.l.c. with electrochemical detection in the reduc tive mode. Results Mean (+/- s.d.) maximum concentrations of ARM, 310 +/- 153 mu g l(-1), were reached 1.88 +/- 0.21 h after drug intake, Th e mean elimination half-life was 2.00 +/- 0.59 h, and the mean AUC 671 +/- 271 mu g l(-1) h. The mean C-max of DHA, 273 +/- 64 mu g l(-1) wa s observed at 1.92 +/- 0.13 h. The mean AUC of DHA was 753 +/- 233 mu g h l(-1). ARM and DHA were stable at less than or equal to -20 degree s C for at least 4 months in plasma samples. Conclusions The relativel y short half-life of ARM, may be one of the factors responsible for th e 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 degrees C) it is recommended to store them at a temperature of less than or equal to -20 degrees C as early as poss ible after sample collection.