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Severe acute malnutrition (SAM) has been reported to be associated with increased malaria morbidity in Sub-Saharan African children and may affect the pharmacology of antimalarial drugs. This population pharmacokinetic-pharmacodynamic study included 131 SAM and 266 non-SAM children administered artemether-lumefantrine twice daily for 3 days. Lumefantrine capillary plasma concentrations were adequately described by two transit-absorption compartments followed by two distribution compartments. Allometrically scaled body weight and an enzymatic maturation effect were included in the pharmacokinetic model. Mid-upper arm circumference (MUAC) was associated with decreased absorption of lumefantrine (25.4% decrease per 1 cm reduction). Risk of recurrent malaria episodes (i.e. reinfection) were characterised by an interval-censored time-to-event model with a sigmoid EMAX -model describing the effect of lumefantrine. SAM children were at risk of under-exposure to lumefantrine and an increased risk of malaria reinfection compared to well-nourished children. Research on optimised regimens should be considered for malaria treatment in malnourished children. This article is protected by copyright. All rights reserved.

Original publication

DOI

10.1002/cpt.1531

Type

Journal article

Journal

Clin Pharmacol Ther

Publication Date

01/06/2019

Keywords

Lumefantrine, malaria, malnutrition, non-linear mixed effects modelling, population pharmacokinetic-pharmacodynamic model, severe acute malnutrition children