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

Zaloumis, Sophie, Tarning, Joel, Krishna, Sanjeev, Price, Ric N., White, Nicholas, Davis, Timothy, McCaw, James, Olliaro, Piero, Maude, Richard, Kremsner, Peter, Dondorp, Arjen M., Gomes, M., Barnes, Karen and Simpson, Julie (2014). Population pharmacokinetics of intravenous artesunate: a pooled analysis of individual data from patients with severe malaria. Nature,3(11 - Article No. e145):1-9.

Document type: Journal Article
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IRMA ID 84473293xPUB17
Title Population pharmacokinetics of intravenous artesunate: a pooled analysis of individual data from patients with severe malaria
Author Zaloumis, Sophie
Tarning, Joel
Krishna, Sanjeev
Price, Ric N.
White, Nicholas
Davis, Timothy
McCaw, James
Olliaro, Piero
Maude, Richard
Kremsner, Peter
Dondorp, Arjen M.
Gomes, M.
Barnes, Karen
Simpson, Julie
Journal Name Nature
Publication Date 2014
Volume Number 3
Issue Number 11 - Article No. e145
ISSN 0028-0836   (check CDU catalogue  open catalogue search in new window)
Start Page 1
End Page 9
Total Pages 9
Place of Publication United Kingdom
Publisher Nature Publishing Group
HERDC Category C1 - Journal Article (DIISR)
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 adults. Post hoc estimates of DHA exposure were not significantly associated with parasitological outcomes. Comparable DHA exposure in smaller children and adults after i.v. ARS was achieved under a dose modification for intramuscular ARS proposed in a separate analysis of children.
DOI http://dx.doi.org/10.1038/psp.2014.43   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)
 
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