Population pharmacokinetics of intramuscular artesunate in african children with severe malaria: Implications for a practical dosing regimen

Ilse Hendriksen, George Mtove, Alison Kent, Samwel Gesase, Hugh Reyburn, Martha Lemnge, Lindegardh, Nicholas Day, Lorenz Von Seidlein, Nicholas J White, Arjen Dondorp, J TARNING

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)443-450
Number of pages8
JournalClinical Pharmacology and Therapeutics
Volume93
Issue number5
Early online date8 Feb 2013
DOIs
Publication statusPublished - May 2013

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