The pharmacokinetics of intravenous artesunate in adults with severe falciparum malaria
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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.
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.
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.
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.
KeywordsArtesunate Pharmacokinetics Plasmodium falciparum Severe malaria
This study was a part of the Wellcome Trust-Mahidol University Oxford Tropical Medicine Research Programme, funded by the Wellcome Trust of Great Britain. We are very grateful to the Director, doctors and nurses of Mae Sot Hospital, Thanongsak Teewarakulpana, Paktiya Teja-Isavadharm, Kamolrat Silamut, Kesinee Chotivanich, Sayan Langla, Kongpop Pupae, Nitirat Thima, Niklas Lindegårdh and Nicholas Day for their help and advice.
[The study complies with the laws of Thailand inclusive of ethical approval].
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