Population Pharmacokinetics of Intramuscular Artesunate in African Children With Severe Malaria: Implications for a Practical Dosing Regimen

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...

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Main Authors:	Hendriksen, ICE, Mtove, G, Kent, A, Gesase, S, Reyburn, H, Lemnge, M M, Lindegardh, N, Day, N P J, von Seidlein, L, White, N J, Dondorp, A M, Tarning, J
Format:	Online
Language:	English
Published:	Nature Publishing Group 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3630454/

id	pubmed-3630454
recordtype	oai_dc
spelling	pubmed-36304542013-05-01 Population Pharmacokinetics of Intramuscular Artesunate in African Children With Severe Malaria: Implications for a Practical Dosing Regimen Hendriksen, ICE Mtove, G Kent, A Gesase, S Reyburn, H Lemnge, M M Lindegardh, N Day, N P J von Seidlein, L White, N J Dondorp, A M Tarning, J Articles 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. Nature Publishing Group 2013-05 2013-03-20 /pmc/articles/PMC3630454/ /pubmed/23511715 http://dx.doi.org/10.1038/clpt.2013.26 Text en Copyright © 2013 American Society of Clinical Pharmacology and Therapeutics http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Hendriksen, ICE Mtove, G Kent, A Gesase, S Reyburn, H Lemnge, M M Lindegardh, N Day, N P J von Seidlein, L White, N J Dondorp, A M Tarning, J
spellingShingle	Hendriksen, ICE Mtove, G Kent, A Gesase, S Reyburn, H Lemnge, M M Lindegardh, N Day, N P J von Seidlein, L White, N J Dondorp, A M Tarning, J Population Pharmacokinetics of Intramuscular Artesunate in African Children With Severe Malaria: Implications for a Practical Dosing Regimen
author_facet	Hendriksen, ICE Mtove, G Kent, A Gesase, S Reyburn, H Lemnge, M M Lindegardh, N Day, N P J von Seidlein, L White, N J Dondorp, A M Tarning, J
author_sort	Hendriksen, ICE
title	Population Pharmacokinetics of Intramuscular Artesunate in African Children With Severe Malaria: Implications for a Practical Dosing Regimen
title_short	Population Pharmacokinetics of Intramuscular Artesunate in African Children With Severe Malaria: Implications for a Practical Dosing Regimen
title_full	Population Pharmacokinetics of Intramuscular Artesunate in African Children With Severe Malaria: Implications for a Practical Dosing Regimen
title_fullStr	Population Pharmacokinetics of Intramuscular Artesunate in African Children With Severe Malaria: Implications for a Practical Dosing Regimen
title_full_unstemmed	Population Pharmacokinetics of Intramuscular Artesunate in African Children With Severe Malaria: Implications for a Practical Dosing Regimen
title_sort	population pharmacokinetics of intramuscular artesunate in african children with severe malaria: implications for a practical dosing regimen
description	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.
publisher	Nature Publishing Group
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3630454/
_version_	1611971313374593024

Population Pharmacokinetics of Intramuscular Artesunate in African Children With Severe Malaria: Implications for a Practical Dosing Regimen

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