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To investigate the pharmacokinetic and pharmacodynamic properties of artesunate (ARTS) and its active metabolite dihydroartemisinin (DHA) in Plasmodium vivax infections, 12 male Vietnamese adults with slide-positive vivax malaria received either intravenous ARTS (120 mg; group 1) or oral ARTS (100 mg; group 2) with the alternative preparation given 8 hr later in a randomized, open, cross-over study. Following intravenous injection, ARTS had a peak plasma drug concentration (Cmax) of 35.6 microM (13.7 mg/L), an elimination half-life (t1/2) of 2.2 min, a clearance (CL) of 3.0 L/hr/kg, and a volume of distribution (V) of 0.16 L/kg. Dihydroartemisinin had a Cmax of 7.7 microM (2.2 mg/L), a tmax of 8 min, a t1/2 of 37 min, an apparent CL of 1.1 L/hr/kg, and an apparent V of 0.9 L/kg. Following oral ARTS, the mean relative bioavailability of DHA was 85%, the Cmax was 3.0 microM (0.85 mg/L), the tmax was 75 min, and t1/2 was 40 min. The mean time to 50% reduction in the parasite count (PCT50) and median fever clearance time were 3 hr and 16 hr, respectively. Following intravenous ARTS (group 1), the PCT50 for total parasites, rings, trophozoites, and gametocytes was 3.3 hr, 3.2 hr, 4.0 hr, and 3.6 hr, respectively. This study confirms that ARTS is effective against P. vivax, with rapid clearance of sexual and asexual forms of the parasite. Artesunate is a suitable initial treatment for vivax malaria, or when the plasmodial species cannot be reliably identified.