title: Oil-Fortified Maize Porridge Increases Absorption of Lumefantrine in Children with Uncomplicated Falciparum Malaria.
abstract: Artemether-lumefantrine (AL) is a first-line treatment for uncomplicated malaria. Absorption of lumefantrine (LUM) is fat dependent, and in children, intake is recommended with milk. We investigated whether oil-fortified maize porridge can be an alternative when milk is not available. In an open-label pharmacokinetic study, Ugandan children <5 years with uncomplicated Plasmodium falciparum malaria were randomized to receive standard six-dose AL treatment [one tablet (20 mgA/120 mg LUM) if <15 kg and two tablets if >15 kg] with milk (A) or maize porridge plus oil (B). Parametric two-sample t-test was used to compare relative oral LUM bioavailability. The primary end-point was LUM exposure till 8 hr after the first dose (AUC0-8 hr). Secondary outcome included day 7 concentrations (d7LUM), LUM exposure between days 7 and 28 (AUCd7-28) and day 28 PCR-adjusted parasitological response. Evaluable children (n = 33) included 16 in arm A and 17 in arm B. The AUC0-8 hrwas comparable between A and B [geometric mean (95% CI): 6.01 (3.26-11.1) versus 6.26 (4.5-8.43) hr*μg/mL, p = 0.9]. Less interindividual variability in AUC0-8 hrwas observed in B (p = 0.01), but d7LUMand AUCd7-28were comparable. Children receiving two tablets had significantly higher exposure than those receiving one tablet [median d7LUM(505 versus 289 ng/mL, p = 0.02) and AUCd7-28(108 versus 41 hr*μg/mL, p = 0.006)]. One parasitological failure (d28 recrudescence) was observed. Our findings suggest that oil-fortified maize porridge can be an alternative to milk in augmenting absorption of LUM. The lower LUM exposure observed in children dosed with one AL tablet needs further attention.
authors.affiliation: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institute Huddinge, Stockholm, Sweden.|Department of Pharmacology and Therapeutics, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: Norah
authors.initials: N
authors.lastname: Mwebaza
authors.affiliation: Markus Jerling Consulting AB, Bromma, Sweden.
authors.forename: Markus
authors.initials: M
authors.lastname: Jerling
authors.affiliation: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institute Huddinge, Stockholm, Sweden.
authors.forename: Lars L
authors.initials: LL
authors.lastname: Gustafsson
authors.affiliation: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institute Huddinge, Stockholm, Sweden.
authors.forename: Antero V
authors.initials: AV
authors.lastname: Silva
authors.affiliation: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institute Huddinge, Stockholm, Sweden.
authors.forename: Anton
authors.initials: A
authors.lastname: Pohanka
authors.affiliation: Department of Pharmacology and Therapeutics, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: Celestino
authors.initials: C
authors.lastname: Obua
authors.affiliation: Department of Pharmacology and Therapeutics, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: Paul
authors.initials: P
authors.lastname: Waako
authors.affiliation: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institute Huddinge, Stockholm, Sweden.
authors.forename: Olof
authors.initials: O
authors.lastname: Beck
authors.affiliation: Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.|Unit of Infectious Diseases, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden.
authors.forename: Manijeh Vafa
authors.initials: MV
authors.lastname: Homann
authors.affiliation: Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.|Unit of Infectious Diseases, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Färnert
authors.affiliation: Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.|Unit of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institute, Stockholm, Sweden.
authors.forename: Urban
authors.initials: U
authors.lastname: Hellgren
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D002675:Child, Preschool; D004983:Ethanolamines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018565:Food-Drug Interactions; D006801:Humans; D007223:Infant; D000078102:Lumefantrine; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D008892:Milk; D010938:Plant Oils / Q000008:administration & dosage; D013607:Tablets; D013997:Time Factors; D016896:Treatment Outcome; D014454:Uganda; D003313:Zea mays
chemical_list: D000962:Antimalarials; D004983:Ethanolamines; D005449:Fluorenes; D010938:Plant Oils; D013607:Tablets; D000078102:Lumefantrine