The pharmacokinetics of a single dose of artemisinin in healthy Vietnamese subjects.

The pharmacokinetics of artemisinin was studied in 12 healthy male Vietnamese subjects after a single, 500-mg, oral dose. A total of 14 plasma samples per subject was obtained up to 48 hr after drug intake. Measurement of artemisinin concentration was performed by high-performance liquid chromatography with electrochemical detection. Tolerance was evaluated by recording subjective and objective findings including repeated physical examination, routine blood investigation, and electrocardiograms. Fitting of the concentration-time curve and pharmacokinetic calculations revealed the following results: a mean +/- SD volume of distribution/dose ratio of 19.4 +/- 6.9 L/kg, a mean +/- SD absorption half-life of 0.58 +/- 0.54 hr with a mean +/- SD calculated maximum concentration of 391 +/- 147 micrograms/L occurring at 1.81 +/- 0.73 hr after drug intake. Elimination was rapid, with a mean +/- SD elimination half-life of 2.59 +/- 0.55 hr. Peak concentrations were sufficient with regard to antimalarial activity although bioavailability appears to be very low. The relatively small interindividual variation in pharmacokinetics does not seem to be of clinical significance. Tolerance to the single dose of artemisinin was good: no adverse effects were detected. Based on these results, a treatment schedule of 2 x 500 mg of artemisinin (oral dose) per day can be advised. This will result in adequate antimalarial plasma concentrations, despite poor bioavailability, and rapid elimination.