title: Comparable lumefantrine oral bioavailability when co-administered with oil-fortified maize porridge or milk in healthy volunteers.
abstract: Co-administration of artemether-lumefantrine with milk is recommended to improve lumefantrine (L) absorption but milk may not be available in resource-limited settings. This study explored the effects of cheap local food in Uganda on oral bioavailability of lumefantrine relative to milk. In an open-label, four-period crossover study, 13 healthy adult volunteers were randomized to receive a single oral dose of artemether-lumefantrine (80 mg artemether/480 mg lumefantrine) with water, milk, maize porridge or maize porridge with oil on separate occasions. Plasma lumefantrine was assayed using high-performance liquid chromatography with ultraviolet detection. Pharmacokinetic exposure parameters were determined by non-compartmental methods using WinNonlin. Peak concentrations (Cmax ) and area under concentration-time curve restricted to 48 hr after single dosing (AUC(0-48) ) were selected for relative bioavailability evaluations using confidence interval approach for average bioequivalence. Lumefantrine exposure was comparable in milk and maize porridge plus oil study groups. When artemether-lumefantrine was administered with maize porridge plus oil, average bioequivalence ranges (means ratios 90% CI, 0.84-1.88 and 0.85-1.69 for Cmax and AUC(0-48) , respectively) were within and exceeded acceptance ranges relative to milk (90% CI, 0.80-1.25). Both fasted and maize porridge groups demonstrated similarly much lower ranges of lumefantrine exposures (bioinequivalence) relative to milk. If milk is not available, it is thus possible to recommend fortification of carbohydrate-rich food with little fat (maize porridge plus vegetable oil) to achieve similarly optimal absorption of lumefantrine after artemether-lumefantrine administration.
authors.affiliation: Department of Pharmacology and Therapeutics, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda. mwebno@yahoo.com
authors.forename: Norah
authors.initials: N
authors.lastname: Mwebaza
authors.forename: Markus
authors.initials: M
authors.lastname: Jerling
authors.forename: Lars L
authors.initials: LL
authors.lastname: Gustafsson
authors.forename: Celestino
authors.initials: C
authors.lastname: Obua
authors.forename: Paul
authors.initials: P
authors.lastname: Waako
authors.forename: Margarita
authors.initials: M
authors.lastname: Mahindi
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ntale
authors.forename: Olof
authors.initials: O
authors.lastname: Beck
authors.forename: Urban
authors.initials: U
authors.lastname: Hellgren
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000493:pharmacokinetics*; D019540:Area Under Curve; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000493:pharmacokinetics*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004338:Drug Combinations; D004983:Ethanolamines / Q000493:pharmacokinetics*; D005260:Female; D005449:Fluorenes / Q000493:pharmacokinetics*; D018565:Food-Drug Interactions; D006801:Humans; D008297:Male; D008892:Milk; D010938:Plant Oils / Q000494:pharmacology*; D014454:Uganda; D003313:Zea mays
chemical_list: D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D010938:Plant Oils