Absence of time-dependent artesunate pharmacokinetics in healthy subjects during 5-day oral administration.

AIM

The aim of the present study was to investigate the existence of time-dependent pharmacokinetics of artesunate (ARS) during 5 consecutive days of oral administration to 10 healthy Vietnamese subjects (aged 21-52 years and weighing 49-90 kg).

METHODS

Each volunteer received 200 mg oral doses of ARS once daily for 5 consecutive days. Blood samples (3 ml each) were collected on days 1 and 5 at 0 (before dosing), 0.5, 1, 2, 3, 4, and 6 h after drug administration. During days 2, 3, and 4, the same volumes of blood were collected at 0, 1, 2, and 4 h after dosing. Plasma ARS and dihydroartemisinin (DHA) were measured using high-performance liquid chromatography-mass spectrometry (LC-MS).

RESULTS

Results did not show evidence of time-dependency for ARS or the active plasma metabolite DHA. There were no differences in the concentrations of ARS and DHA at all sampling times on days 1 and 5. In addition, the pharmacokinetics of both compounds were similar on days 1 and 5. This finding confirms that the enzyme auto-induction in drug metabolism may not be characteristic of the endoperoxide sesquiterpene antimalarial group.