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

Zaloumis, SG; Tarning, J; Krishna, S; Price, RN; White, NJ; Davis, TM; McCaw, JM; Olliaro, P; Maude, RJ; Kremsner, P; et al. Zaloumis, SG; Tarning, J; Krishna, S; Price, RN; White, NJ; Davis, TM; McCaw, JM; Olliaro, P; Maude, RJ; Kremsner, P; Dondorp, A; Gomes, M; Barnes, K; Simpson, JA (2014) Population pharmacokinetics of intravenous artesunate: a pooled analysis of individual data from patients with severe malaria. CPT: Pharmacometrics and Systems Pharmacology, 3. ISSN 2163-8306 https://doi.org/10.1038/psp.2014.43
SGUL Authors: Krishna, Sanjeev

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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 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.

Item Type: Article
Additional Information: © 2014 ASCPT. This work is licensed under a Creative Commons Attribution 3.0 Unported License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: CPT: Pharmacometrics and Systems Pharmacology
Article Number: e145
ISSN: 2163-8306
Language: eng
Dates:
DateEvent
November 2014Published
Projects:
Project IDFunderFunder ID
091625Wellcome TrustUNSPECIFIED
093956Wellcome TrustUNSPECIFIED
PubMed ID: 25372510
Go to PubMed abstract
URI: http://sgultest.da.ulcc.ac.uk/id/eprint/107328
Publisher's version: https://doi.org/10.1038/psp.2014.43

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