A pharmacokinetic and pharmacodynamic study of intravenous vsoral artesunate in uncomplicated falciparum malaria

Aims To obtain comprehensive pharmacokinetic and pharmacodynamic data for artesunate (ARTS) and its active metabolite dihydroartemisinin (DHA) following i.v. and oral administration of ARTS to patients with acute, uncomplicated falciparum malaria. 9.3 m m (2.64 mg l − 1 ), t 1/2 = 40 min, CL = 0.75 l h − 1 kg − 1 and V = 0.76 l kg − 1 . Following oral ARTS, relative bioavailability of DHA was 82%, C max was 2.6 m m (0.74 mg l − 1 ), t 1/2 = 39 min, and MAT = 67 min. Overall, the PCT 50 and fever clearance time (FCT) were 6.5 h and 24 h, respectively. There was no correlation between PCT 50 or FCT and AUC, C max or MRT for DHA. Conclusions Despite rapid clearance of ARTS and DHA in patients with uncomplicated falciparum malaria, prompt parasite and fever clearance were achieved. High relative bioavailability of DHA following oral ARTS administration, and clinical outcomes comparable with those after i.v. ARTS, support the use of the oral formulation in the primary care setting.

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