Severe Acute Malnutrition Results in Lower Lumefantrine Exposure in Children Treated With Artemether-Lumefantrine for Uncomplicated Malaria
© 2019 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics Severe acute malnutrition (SAM) has been reported to be associated with increased malaria morbidity in Sub-Saharan African child...
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th-mahidol.512932020-01-27T16:20:41Z Severe Acute Malnutrition Results in Lower Lumefantrine Exposure in Children Treated With Artemether-Lumefantrine for Uncomplicated Malaria Palang Chotsiri Lise Denoeud-Ndam Elisabeth Baudin Ousmane Guindo Halimatou Diawara Oumar Attaher Michiel Smit Philippe J. Guerin Ogobara K. Doumbo Lubbe Wiesner Karen I. Barnes Richard M. Hoglund Alassane Dicko Jean Francois Etard Joel Tarning University of Bamako Faculty of Medicine, Pharmacy and Odonto-Stomatology Epicentre Mahidol University Nuffield Department of Clinical Medicine Inserm University of Cape Town WorldWide Antimalarial Resistance Network (WWARN) Medicine © 2019 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics 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 (PK)-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 PK model. Mid-upper arm circumference was associated with decreased absorption of lumefantrine (25.4% decreased absorption per 1 cm reduction). Risk of recurrent malaria episodes (i.e., reinfection) were characterized by an interval-censored time-to-event model with a sigmoid maximum-effect model describing the effect of lumefantrine. SAM children were at risk of underexposure to lumefantrine and an increased risk of malaria reinfection compared with well-nourished children. Research on optimized regimens should be considered for malaria treatment in malnourished children. 2020-01-27T09:20:41Z 2020-01-27T09:20:41Z 2019-12-01 Article Clinical Pharmacology and Therapeutics. Vol.106, No.6 (2019), 1299-1309 10.1002/cpt.1531 15326535 00099236 2-s2.0-85069928114 https://repository.li.mahidol.ac.th/handle/123456789/51293 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85069928114&origin=inward |
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Medicine Palang Chotsiri Lise Denoeud-Ndam Elisabeth Baudin Ousmane Guindo Halimatou Diawara Oumar Attaher Michiel Smit Philippe J. Guerin Ogobara K. Doumbo Lubbe Wiesner Karen I. Barnes Richard M. Hoglund Alassane Dicko Jean Francois Etard Joel Tarning Severe Acute Malnutrition Results in Lower Lumefantrine Exposure in Children Treated With Artemether-Lumefantrine for Uncomplicated Malaria |
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© 2019 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics 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 (PK)-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 PK model. Mid-upper arm circumference was associated with decreased absorption of lumefantrine (25.4% decreased absorption per 1 cm reduction). Risk of recurrent malaria episodes (i.e., reinfection) were characterized by an interval-censored time-to-event model with a sigmoid maximum-effect model describing the effect of lumefantrine. SAM children were at risk of underexposure to lumefantrine and an increased risk of malaria reinfection compared with well-nourished children. Research on optimized regimens should be considered for malaria treatment in malnourished children. |
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University of Bamako Faculty of Medicine, Pharmacy and Odonto-Stomatology |
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University of Bamako Faculty of Medicine, Pharmacy and Odonto-Stomatology Palang Chotsiri Lise Denoeud-Ndam Elisabeth Baudin Ousmane Guindo Halimatou Diawara Oumar Attaher Michiel Smit Philippe J. Guerin Ogobara K. Doumbo Lubbe Wiesner Karen I. Barnes Richard M. Hoglund Alassane Dicko Jean Francois Etard Joel Tarning |
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Article |
author |
Palang Chotsiri Lise Denoeud-Ndam Elisabeth Baudin Ousmane Guindo Halimatou Diawara Oumar Attaher Michiel Smit Philippe J. Guerin Ogobara K. Doumbo Lubbe Wiesner Karen I. Barnes Richard M. Hoglund Alassane Dicko Jean Francois Etard Joel Tarning |
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Palang Chotsiri |
title |
Severe Acute Malnutrition Results in Lower Lumefantrine Exposure in Children Treated With Artemether-Lumefantrine for Uncomplicated Malaria |
title_short |
Severe Acute Malnutrition Results in Lower Lumefantrine Exposure in Children Treated With Artemether-Lumefantrine for Uncomplicated Malaria |
title_full |
Severe Acute Malnutrition Results in Lower Lumefantrine Exposure in Children Treated With Artemether-Lumefantrine for Uncomplicated Malaria |
title_fullStr |
Severe Acute Malnutrition Results in Lower Lumefantrine Exposure in Children Treated With Artemether-Lumefantrine for Uncomplicated Malaria |
title_full_unstemmed |
Severe Acute Malnutrition Results in Lower Lumefantrine Exposure in Children Treated With Artemether-Lumefantrine for Uncomplicated Malaria |
title_sort |
severe acute malnutrition results in lower lumefantrine exposure in children treated with artemether-lumefantrine for uncomplicated malaria |
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2020 |
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https://repository.li.mahidol.ac.th/handle/123456789/51293 |
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1763497194859528192 |