Comparative pharmacokinetic study of oral and rectal formulations of artesunic acid in healthy volunteers

OBJECTIVE: A single cross-over, comparative pharmacokinetic study of oral and rectal formulations of 200 mg artesunic acid in 12 healthy Malaysian volunteers is reported.

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.