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    Mar 06, 2021
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    Severe acute malnutrition results in lower lumefantrine exposure in children treated with artemether-lumefantrine for uncomplicated malaria

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    Chotsiri et al - 2019 - Severe ...
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    Authors
    Chotsiri, P
    Denoeud-Ndam, L
    Baudin, E
    Guindo, O
    Diawara, H
    Attaher, O
    Smit, M
    Guerin, PJ
    Duombo, OK
    Weisner, L
    Barnes, KI
    Hoglund, RM
    Dicko, A
    Etard, JF
    Tarning, J
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    Issue Date
    2019-06-01
    Submitted date
    2019-06-20
    
    Metadata
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    Journal
    Clinical Pharmacology & Therapeutics
    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 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.
    Publisher
    American Society for Clinical Pharmacology and Therapeutics
    URI
    http://hdl.handle.net/10144/619406
    Language
    en
    Collections
    Malaria

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