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 electro-chemical detection in the reductive mode.
RESULTS: Mean (+/- s.d.) maximum concentrations of ARM, 310 +/- 153 micrograms 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 micrograms l-1 h. The mean Cmax of DHA, 273 +/- 64 micrograms l-1 was observed at 1.92 +/- 0.13 h. The mean AUC of DHA was 753 +/- 233 micrograms h l-1'. ARM and DHA were stable at < or = -20 degrees 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 degrees C) it is recommended to store them at a temperature of < or = -20 degrees C as early as possible after sample collection.
METHODS: Plasma concentrations of artesunic acid and dihydroartemisinin were determined simultaneously by HPLC with electrochemical detection. The test drug was well tolerated and no undesirable adverse effects were observed.
RESULTS: Comparison of pharmacokinetic parameters of artesunic acid after oral and rectal administration showed statistically significant differences in t(max) and AUC, with no changes for Cmax and t1/2. As for dihydroartemisinin, differences were observed for t(max) and Cmax but not for AUC.
CONCLUSION: There appear to be pharmacokinetic differences between oral and rectal modes of administration. The significance of these findings should be explored in malaria patients before appropriate therapeutic regimens are devised.