DDMODEL00000309: Population pharmacokinetic properties of lumefantrine in malnourished children

  public model
Short description:
Population pharmacokinetics of lumefantrine in severely acute malnourished children infected with uncomplicated falciparum malaria
Original code
  • Severe Acute Malnutrition Results in Lower Lumefantrine Exposure in Children Treated With Artemether-Lumefantrine for Uncomplicated Malaria.
  • Chotsiri P, Denoeud-Ndam L, Baudin E, Guindo O, Diawara H, Attaher O, Smit M, Doumbo OK, Wiesner L, Barnes KI, Hoglund RM, Dicko A, Etard JF
  • Clinical pharmacology and therapeutics, 6/2019
  • Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
  • 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.
Joel Tarning
Context of model development: Patient Population Selection and Bridging between Population (Pediatrics, Elderly, Obese); Variability sources in PK and PD (CYP, Renal, Biomarkers);
Long technical model description: A detailed explanation of the model can be found in the published manuscript, Severe Acute Malnutrition Results in Lower Lumefantrine Exposure in Children Treated With Artemether-Lumefantrine for Uncomplicated Malaria (published at Clinical Pharmacology & Therapeutics);
Model compliance with original publication: Yes;
Model implementation requiring submitter’s additional knowledge: No;
Modelling context description: In Africa, malaria and malnutrition are the most common co-morbidities in children. During malnutrition the absorption of nutrients can be limited and in children malnutrition might result in long-term physiological and developmental alterations. Lumefantrine is an antimalarial drug which is administered together with a high fat meal to enhance its absorption. Therefore, in severe malnourished individuals lumefantrine absorption might be altered. The aim of this model was to describe the pharmacokinetic properties of lumefantrine in severe acute malnourished children;
Modelling task in scope: estimation;
Nature of research: Clinical research & Therapeutic use;
Therapeutic/disease area: Anti-infectives;
Annotations are correct.
This model is not certified.
  • Model owner: Joel Tarning
  • Submitted: Oct 3, 2019 9:14:35 AM
  • Last Modified: Oct 3, 2019 9:14:35 AM
  • Version: 4 public model Download this version
    • Submitted on: Oct 3, 2019 9:14:35 AM
    • Submitted by: Joel Tarning
    • With comment: Updated model annotations.