The pharmacokinetics of intravenous artesunate in adults with severe falciparum malaria

Objective Intravenous artesunate is commonly used in the emergency treatment of patients with severe falciparum malaria in Asia. The choice of doses used has been empirical. To inform dosage recommendations we assessed the pharmacokinetics of intravenous artesunate after the first dose. Methods As part of a clinical trial of artesunate in adults with severe falciparum malaria in western Thailand, we assayed plasma concentrations of artesunate and the principal biologically active metabolite dihydroartemisinin (DHA) in 17 patients given an initial dose of 2.4 mg/kg body weight of intravenous artesunate. Drug levels were measured using high performance liquid chromatography with mass spectroscopy-electrospray ionisation detection. Results Median (range) observed DHA Cmax was 2128 (513-5789) nmol/L, elimination half-life was 0.34 (0.14-0.87) h, and the time to the last detectable DHA was 2 h. Conclusion The large inter-individual variability (10 fold) in DHA Cmax and AUC in patients with potentially lethal, severe malaria, suggests that 2.4 mg/kg should be the minimum daily dose in severe malaria.