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Title: Population pharmacokinetics of intravenous artesunate: A pooled analysis of individual data from patients with severe malaria
Authors: S. G. Zaloumis
J. Tarning
S. Krishna
R. N. Price
N. J. White
T. M.E. Davis
J. M. McCaw
P. Olliaro
R. J. Maude
P. Kremsner
A. Dondorp
M. Gomes
K. Barnes
J. A. Simpson
University of Melbourne
Mahidol University
St George's University of London
Nuffield Department of Clinical Medicine
University of Western Australia
Organisation Mondiale de la Sante
Albert Schweitzer Hospital
Universitat Tubingen
University of Cape Town
Keywords: Mathematics;Medicine
Issue Date: 1-Jan-2014
Citation: CPT: Pharmacometrics and Systems Pharmacology. Vol.3, No.11 (2014)
Abstract: © 2014 ASCPT All rights reserved. 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.
ISSN: 21638306
Appears in Collections:Scopus 2011-2015

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