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Title: Population pharmacokinetics of intramuscular artesunate in african children with severe malaria: Implications for a practical dosing regimen
Authors: I. C.E. Hendriksen
G. Mtove
A. Kent
S. Gesase
H. Reyburn
M. M. Lemnge
N. Lindegardh
N. P.J. Day
L. Von Seidlein
N. J. White
A. M. Dondorp
J. Tarning
Mahidol University
University of Oxford
National Institute for Medical Research Tanga
Joint Malaria Programme
London School of Hygiene & Tropical Medicine
Menzies School of Health Research
Keywords: Medicine;Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-May-2013
Citation: Clinical Pharmacology and Therapeutics. Vol.93, No.5 (2013), 443-450
Abstract: Parenteral artesunate (ARS) is the drug of choice for the treatment of severe malaria. Pharmacokinetics data on intramuscular ARS are limited with respect to the main treatment group that carries the highest mortality, namely, critically ill children with severe malaria. A population pharmacokinetic study of ARS and dihydroartemisinin (DHA) was conducted from sparse sampling in 70 Tanzanian children of ages 6 months to 11 years. All the children had been admitted with severe falciparum malaria and were treated with intramuscular ARS (2.4 mg/kg at 0, 12, and 24 h). Venous plasma concentration-time profiles were characterized using nonlinear mixed-effects modeling (NONMEM). A one-compartment disposition model accurately described first-dose population pharmacokinetics of ARS and DHA. Body weight significantly affected clearance and apparent volume of distribution (P < 0.001), resulting in lower ARS and DHA exposure levels in smaller children. An adapted dosing regimen including a practical dosing table per weight band is proposed for young children based on the pharmacokinetic model. © 2013 American Society for Clinical Pharmacology and Therapeutics.
ISSN: 15326535
Appears in Collections:Scopus 2011-2015

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