Pharmacokinetics of Artemisinin and Artesunate after Oral Administration in Healthy Volunteers

Abstract

This study was designed to determine the pharmacokinetic parameters of a new pharmaceutical form of artemisinin (a natural substance extracted from the Artemisia annua L. plant) and of one of its derivatives, artesunate, a semisuccinate of 12-hydroxy-artemisinin. These two compounds 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 pharmacokinetic studies. For artemisinin, the mean pharmacokinetic parameters were maximum drug concentration (Cmax) = 0.36 µg/ml; peak time (tmax) = 100 min; appearance half-life (t1/2 max) = 0.62 hr; distribution half-life (t1/2α) = 2.61 hr; decline half-life (t1/2β) = 4.34 hr; and total area under the concentration-time curve (AUC) = 1.19 µg.hr/ml. For artesunate, its main metabolite, dihydroartemisinin, was measurable in the plasma. The mean pharmacokinetic parameters for dihydroartemisinin were appearance rate constant (Ka) = 2.11 hr;-1; elimination rate constant (Ke) = 1.18 hr-1; biotransformation half-life = 0.33 hr; elimination half-life = 0.65 hr; and AUC = 0.74 µg.hr/ml. Both pharmaceutical forms were well-tolerated and no undesirable side effects were observed in any of the subjects.