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Free Content The effect of food consumption on lumefantrine bioavailability in African children receiving artemether–lumefantrine crushed or dispersible tablets (Coartem®) for acute uncomplicated Plasmodium falciparum malaria

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Abstract:

Summary Objectives  Artemether–lumefantrine (AL) is first-line treatment for uncomplicated malaria in many African countries. Concomitant food consumption may affect absorption of lumefantrine but data in the most important target population, i.e. children, are lacking. Therefore, we evaluated the effect of food intake on oral lumefantrine bioavailability in African children with malaria. Methods  In a randomised, investigator-blinded, multicentre phase III efficacy trial, 899 infants and children with acute uncomplicated malaria received six doses of AL according to body weight over 3 days either as crushed tablets (Coartem) or as dispersible tablets. Single blood samples were obtained for lumefantrine plasma concentration determination in a subset of 621 patients, and a two-compartment pharmacokinetic model was constructed. Results  The mean observed lumefantrine plasma concentration for crushed tablet and dispersible tablet, respectively, was 100% and 55% higher with a concomitant meal at the time of dose intake than when taken alone. Similarly, consumption of milk (the most common meal) increased model-estimated lumefantrine bioavailability by 57% (90% CI: 29–96%) with crushed tablets and 65% (90% CI: 28–109%) with dispersible tablets compared to no food. The 28-day PCR-corrected cure rate (primary study endpoint) in the evaluable population was 582/587 [99.1% (95% CI: 98.0–99.7%)] and was not related to food intake. Conclusions  AL was highly efficacious. Concomitant food intake increased lumefantrine absorption in children with malaria.

French
Objectifs: 

l’artéméther-luméfantrine (AL) est un traitement de première intention contre la malaria sans complications dans de nombreux pays africains. La consommation concomitante d’aliments peu affecter l’absorption de la luméfantrine, mais des données sur la population cible la plus importante i.e. les enfants, font défaut. Par conséquent, nous avons évalué l’effet de la prise alimentaire sur la biodisponibilité orale de la luméfantrine chez des enfants africains atteints de malaria. Méthodes: 

Dans une étude d’efficacité randomisée, aveugle pour l’investigateur, multicentrique de phase III, 899 nourrissons et enfants atteints de malaria aigüe àPlasmodium falciparum non compliquée ont reçu six doses d’AL en fonction du poids du corps pendant 3 jours, soit en comprimés écrasés (Coartem®) ou sous forme de comprimés dispersibles. Des échantillons uniques de sang ont été prélevés pour la détermination de la concentration plasmatique de luméfantrine dans un sous-ensemble de 621 patients et un modèle pharmacocinétique bi compartimental a été construit. Résultats: 

Les concentrations plasmatiques moyennes de luméfantrine observées pour les comprimés écrasés et les comprimés dispersibles étaient de 100% et 55% respectivement plus élevée avec un repas concomitant au moment de la prise de la dose que lorsqu’ils étaient pris seuls. De même, la consommation de lait (le repas le plus commun) augmentait la biodisponibilité luméfantrine estimée par le model de 57% (IC90%: 29-96) avec les comprimés écrasés et 65% (IC90%: 28-109) avec les comprimés dispersibles, comparativement à l’absence de nourriture. Le taux de guérison au jour 28 corrigé par la PCR (critère d’évaluation primaire de l’étude) dans la population évaluable était de 582/587 (99,1% (IC95%: 98.0-99.7%)) et n’était pas liéà la prise alimentaire. Conclusions: 

AL était très efficace. La prise concomitante d’aliments augmente l’absorption de la luméfantrine chez les enfants atteints de malaria.

Keywords: Coartem; Lumefantrina; alimentos; artemeter; artemether; artéméther; bioavailability; biodisponibilidad; biodisponibilité; farmacocinética; food; lumefantrine; luméfantrine; nourriture; pharmacocinétique; pharmacokinetics

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1365-3156.2010.02477.x

Affiliations: 1:  Department of Modeling and Simulation, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA 2:  Manhiça Health Research Centre, Manhiça, Mozambique 3:  Unit of Infectious Diseases, Karolinska University Hospital/Karolinska Institutet, Stockholm, Sweden 4:  Kenya Medical Research Institute, Centre for Vector Biology and Control Research, Kisumu, Kenya 5:  Kenya Medical Research Institute/Wellcome Trust Research Programme, Kilifi, Kenya 6:  Kenya Medical Research Institute/Walter Reed U.S. Army Institute, Kisumu, Kenya 7:  Molecular Epidemiology and Drug Resistance Unit, Malaria Research and Training Center, Faculty of Medicine, Pharmacy and Odonto-Stomatology, Bamako, Mali 8:  Institute of Tropical Medicine, Antwerp, Belgium 9:  Global Program Tropical Medicine, Novartis Pharma AG, Basel, Switzerland 10:  Translational Sciences, Novartis NIBR, Basel, Switzerland

Publication date: April 1, 2010

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