Pharmacogenetics

European Journal of Clinical Pharmacology

, Volume 62, Issue 12, pp 1003-1009

The pharmacokinetics of intravenous artesunate in adults with severe falciparum malaria

  • Paul N. NewtonAffiliated withFaculty of Tropical Medicine, Mahidol UniversityCentre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital
  • , Karen I. BarnesAffiliated withDivision of Clinical Pharmacology, University of Cape Town
  • , Peter J. SmithAffiliated withDivision of Clinical Pharmacology, University of Cape Town
  • , Alicia C. EvansAffiliated withDivision of Clinical Pharmacology, University of Cape Town
  • , Wirongrong ChierakulAffiliated withFaculty of Tropical Medicine, Mahidol University
  • , Ronatrai RuangveerayuthAffiliated withMae Sot Hospital
  • , Nicholas J. WhiteAffiliated withFaculty of Tropical Medicine, Mahidol UniversityCentre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital Email author 

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Abstract

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.

Keywords

Artesunate Pharmacokinetics Plasmodium falciparum Severe malaria