Population pharmacokinetics of intravenous artesunate: A pooled analysis of individual data from patients with severe malaria

SG Zaloumis; J Tarning; S Krishna; RN Price; NJ White; TME Davis; JM McCaw; P Olliaro; RJ Maude; P Kremsner; A Dondorp; M Gomes; K Barnes; JA Simpson

Journal article

Population pharmacokinetics of intravenous artesunate: A pooled analysis of individual data from patients with severe malaria

SG Zaloumis, J Tarning, S Krishna, RN Price, NJ White, TME Davis, JM McCaw, P Olliaro, RJ Maude, P Kremsner, A Dondorp, M Gomes, K Barnes, JA Simpson

Cpt Pharmacometrics and Systems Pharmacology | Published : 2014

DOI: 10.1038/psp.2014.43

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Abstract

There are ∼660,000 deaths from severe malaria each year. Intravenous artesunate (i.v. ARS) is the first-line treatment in adults and children. To optimize the dosing regimen of i.v. ARS, the largest pooled population pharmacokinetic study to date of the active metabolite dihydroartemisinin (DHA) was performed. The pooled dataset consisted of 71 adults and 195 children with severe malaria, with a mixture of sparse and rich sampling within the first 12 h after drug administration. A one-compartment model described the population pharmacokinetics of DHA adequately. Body weight had the greatest impact on DHA pharmacokinetics, resulting in lower DHA exposure for smaller children (6-10 kg) than ad..

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University of Melbourne Researchers

Sophie Zaloumis Author

James McCaw Author

Julie Simpson Author

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Funding Acknowledgements

The work was supported by the National Health and Medical Research Centre of Australia (NHMRC) Project Grant 1025319. S.G.Z. was supported under a NHMRC Centre of Research Excellence grant, ID#1035261, to the Victorian Centre for Biostatistics (ViCBiostat). R.N.P. is a Wellcome Trust Senior Research Fellow in Clinical Science (091625). N.J.W. is a Principal Wellcome Trust Fellow. J.T., R.J.M., and A.D. are supported by the Wellcome Trust as part of the Wellcome Trust-Mahidol University-Oxford Tropical Medicine Research Programme. J.M.Mc.C. is supported by an Australian Research Council Future Fellowship. P.O. is a staff member of the World Health Organization (WHO); M.G. was a WHO staff member at the time of the conduct of the trials and is currently a consultant. P.K. would like to acknowledge Medicines for Malaria Venture for sponsoring the study described in Kremsner et al. 19