Severe acute malnutrition results in lower lumefantrine exposure in children treated with artemether-lumefantrine for uncomplicated malaria.

Auteurs: Chotsiri P Denoeud-Ndam L Baudin E Guindo O Diawara H Attaher O Smit M Guerin PJ Doumbo OK Wiesner L Barnes KI Hoglund RM Dicko A Etard JF Tarning J
Référence de l'article: Clinical pharmacology and therapeutics 2019 Jun 01; (); Array. doi: 10.1002/cpt.1531. Epub 2019 06 01
Lumefantrine malaria malnutrition non-linear mixed effects modelling population pharmacokinetic-pharmacodynamic model severe acute malnutrition children
eng

Abstract

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 E -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.

This article is protected by copyright. All rights reserved.