PHARMACOKINETICS OF ORAL ARTESUNATE IN CHILDREN WITH MODERATELY SEVERE PLASMODIUM-FALCIPARUM MALARIA

The pharmacokinetic properties of oral artesunate (3 mg/kg) were deter mined in 10 Vietnamese children, aged from 6 to 15 years, with acute f alciparum malaria of moderate severity. Plasma concentrations were mea sured using a bioassay and expressed in terms of antimalarial activity equivalent to dihydroartemisinin, the principal biologically active m etabolite. Oral artesunate was absorbed rapidly with a mean time to pe ak plasma bioactivity of 1.7 h (95% confidence interval [95% CI] 0.8-2 .6). There was wide variation in peak plasma concentrations with a mea n value equivalent to 664 ng of dihydroartemisinin/mL (95% CI 387-9410 , range 179-1395) and a four-fold variation in the area under the plas ma concentration-time curves. Elimination from plasma was rapid with a mean (95% CI) half-life of 1.0 h (95% CI 0.8-1.4). Plasma antimalaria l levels were below the limit of detection in all cases by 12 h, despi te the relatively high dose of artesunate used. Oral artesunate is rap idly absorbed and rapidly eliminated in children with moderately sever e malaria but there is considerable variation between individuals.