Efficacy of artemether-lumefantrine in relation to drug exposure in children with and without severe acute malnutrition: an open comparative intervention study in Mali and Niger

• Published in: BMC medicine 2016-10, Vol.14 (1), p.167-167, Article 167
• Main Authors: Denoeud-Ndam, Lise, Dicko, Alassane, Baudin, Elisabeth, Guindo, Ousmane, Grandesso, Francesco, Diawara, Halimatou, Sissoko, Sibiri, Sanogo, Koualy, Traoré, Seydou, Keita, Sekouba, Barry, Amadou, de Smet, Martin, Lasry, Estrella, Smit, Michiel, Wiesner, Lubbe, Barnes, Karen I, Djimde, Abdoulaye A, Guerin, Philippe J, Grais, Rebecca F, Doumbo, Ogobara K, Etard, Jean-François
• Format: Article
• Language: English
• Subjects: Anemia; Antimalarials; Antimalarials - administration & dosage; Antimalarials - pharmacokinetics; Antiparasitic agents; Artemisinins - administration & dosage; Artemisinins - pharmacokinetics; Child, Preschool; Children & youth; Demographic aspects; Dosage and administration; Drug Combinations; Drug dosages; Drug therapy; Ethanolamines - administration & dosage; Ethanolamines - pharmacokinetics; Female; Fluorenes - administration & dosage; Fluorenes - pharmacokinetics; Hemoglobin; Humans; Infant; Malaria; Malaria, Falciparum - drug therapy; Malaria, Falciparum - metabolism; Male; Mali; Malnutrition; Malnutrition in children; Niger; Nutritional status; Patient outcomes; Pharmacokinetics; Physiological aspects; Severe Acute Malnutrition - metabolism; Severe Acute Malnutrition - parasitology; Standard scores
• ISSN: 1741-7015; 1741-7015
• DOI: 10.1186/s12916-016-0716-1

Severe acute malnutrition (SAM) affects almost all organs and has been associated with reduced intestinal absorption of medicines. However, very limited information is available on the pharmacokinetic properties of antimalarial drugs in this vulnerable population. We assessed artemether-lumefantrine (AL) clinical efficacy in children with SAM compared to those without. Children under 5 years of age with uncomplicated P. falciparum malaria were enrolled between November 2013 and January 2015 in Mali and Niger, one third with uncomplicated SAM and two thirds without. AL was administered under direct observation with a fat intake consisting of ready-to-use therapeutic food (RUTF - Plumpy'Nut®) in SAM children, twice daily during 3 days. Children were followed for 42 days, with PCR-corrected adequate clinical and parasitological response (ACPR) at day 28 as the primary outcome. Lumefantrine concentrations were assessed in a subset of participants at different time points, including systematic measurements on day 7. A total of 399 children (360 in Mali and 39 in Niger) were enrolled. Children with SAM were younger than their non-SAM counterparts (mean 17 vs. 28 months, P