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The pharmacokinetics of intravenous artesunate in adults with severe falciparum malaria

  • Pharmacogenetics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

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.

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Acknowledgements

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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Authors and Affiliations

  1. Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd., Bangkok, 10400, Thailand

    Paul N. Newton, Wirongrong Chierakul & Nicholas J. White

  2. Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, UK

    Paul N. Newton & Nicholas J. White

  3. Division of Clinical Pharmacology, University of Cape Town, Cape Town, South Africa

    Karen I. Barnes, Peter J. Smith & Alicia C. Evans

  4. Mae Sot Hospital, Mae Sot, Tak, Thailand

    Ronatrai Ruangveerayuth

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  1. Paul N. Newton
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  2. Karen I. Barnes
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  3. Peter J. Smith
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  4. Alicia C. Evans
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  5. Wirongrong Chierakul
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  6. Ronatrai Ruangveerayuth
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  7. Nicholas J. White
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Corresponding author

Correspondence to Nicholas J. White.

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Newton, P.N., Barnes, K.I., Smith, P.J. et al. The pharmacokinetics of intravenous artesunate in adults with severe falciparum malaria. Eur J Clin Pharmacol 62, 1003–1009 (2006). https://doi.org/10.1007/s00228-006-0203-2

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  • DOI: https://doi.org/10.1007/s00228-006-0203-2

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