Antimalarial bioavailability and disposition of artesunate in acute falciparum malaria

The pharmacokinetic properties of oral and intravenous artesunate (2 mg/kg of body weight) were studied in 19 adult patients with acute uncomplicated Plasmodium falciparum malaria by using a randomized crossover design. A sen sitive bioassay was used to measure the antimalarial activity in plasma whi ch results from artesunate and its principal metabolite, dihydroartemisinin . The oral study was repeated with 15 patients during convalescence. The me an absolute oral bioavailability of the antimalarial agent in patients with acute malaria was 61% (95% confidence interval [CI], 52 to 70%). The absor ption and elimination of oral artesunate were rapid, with a mean eliminatio n half-life of antimalarial activity of 43 min (95% CI, 33 to 53 min). Foll owing oral administration to patients with acute falciparum malaria, peak a ntimalarial activity in plasma and the area under the plasma concentration- time curve were approximately double those during convalescence and the app arent volume of distribution and clearance were approximately half those du ring convalescence (P less than or equal to 0.005). Acute malaria is associ ated with a significant reduction in the clearance of artesunate-associated antimalarial activity.