Population pharmacokinetics of intramuscular artesunate in African children with severe malaria: implications for a practical dosing regimen.


Hendriksen, IC; Mtove, G; Kent, A; Gesase, S; Reyburn, H; Lemnge, MM; Lindegardh, N; Day, NP; von Seidlein, L; White, NJ; Dondorp, AM; Tarning, J; (2013) Population pharmacokinetics of intramuscular artesunate in African children with severe malaria: implications for a practical dosing regimen. Clinical pharmacology and therapeutics, 93 (5). pp. 443-50. ISSN 0009-9236 DOI: https://doi.org/10.1038/clpt.2013.26

[img]
Preview
Text - Published Version
License:

Download (711kB) | Preview

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.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Disease Control
Research Centre: Malaria Centre
PubMed ID: 23511715
Web of Science ID: 317834800026
URI: http://researchonline.lshtm.ac.uk/id/eprint/989865

Statistics


Download activity - last 12 months
Downloads since deposit
232Downloads
312Hits
Accesses by country - last 12 months
Accesses by referrer - last 12 months
Impact and interest
Additional statistics for this record are available via IRStats2

Actions (login required)

Edit Item Edit Item