A PHARMACOKINETIC AND PHARMACODYNAMIC STUDY OF ARTESUNATE FOR VIVAX MALARIA

To investigate the pharmacokinetic and pharmacodynamic properties of a rtesunate (ARTS) and its active metabolite dihydroartemisinin (DHA) in Plasmodium vivax infections, 12 male Vietnamese adults with slide-pos itive 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 intrave nous injection, ARTS had a peak plasma drug concentration (C-max) of 3 5.6 mu M (13.7 mg/L), an elimination half-life (t(1/2)) of 2.2 min, a clearance (CL) of 3.0 L/hr/kg, and a volume of distribution (V) of 0.1 6 L/kg. Dihydroartemisinin had a C-max of 7.7 mu M (2.2 mg/L), a t(max ) of 8 min, a t(1/2) 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 bioavai lability of DHA was 85%, the C-max was 3.0 mu M (0.85 mg/L), the t(max ) was 75 min, and t(1/2) 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 PCT 50 for total parasites, rings, trophozoites, and gametocytes was 3.3 h r, 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 treat ment for vivax malaria, or when the plasmodial species cannot be relia bly identified.