PHARMACOKINETICS OF ARTEMISININ AND ARTESUNATE AFTER ORAL-ADMINISTRATION IN HEALTHY-VOLUNTEERS

This study was designed to determine the pharmacokinetic parameters of a new pharmaceutical form of artemisinin (a natural substance extract ed from the Artemisia annua L. plant) and of one of its derivatives, a rtesunate, a semisuccinate of 12-hydroxy-artemisinin. These two compou nds are widely used in the treatment of malaria. The new oral forms of these two compounds, in 250-mg tablets, were used in two parallel pha rmacokinetic studies. For artemisinin, the mean pharmacokinetic parame ters were maximum drug concentration (C-max) = 0.36 mu g/ml; peak time (t(max)) = 100 min; appearance half-life (t(1/2 max)) = 0.62 hr; dist ribution half-life (t(1/2 alpha)) = 2.61 hr; decline half-life (t(1/2 beta)) = 4.34 hr; and total area under the concentration-time curve (A UG) = 1.19 mu g.hr/ml. For artesunate, its main metabolite, dihydroart emisinin, was measurable in the plasma. The mean pharmacokinetic param eters for dihydroartemisinin were appearance rate constant (K-a) = 2.1 1 hr;(-1); elimination rate constant (K-e) = 1.18 hr(-1); biotransform ation half-life = 0.33 hr; elimination half-life = 0.65 hr; and AUC = 0.74 mu g.hr/ml. Both pharmaceutical forms were well-tolerated and no undesirable side effects were observed in any of the subjects.