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|Title:||How much fat is necessary to optimize lumefantrine oral bioavailability?|
|Authors:||Elizabeth A. Ashley|
Nicholas J. White
Shoklo Malaria Research Unit
Menzies School of Health Research
|Keywords:||Immunology and Microbiology;Medicine|
|Citation:||Tropical Medicine and International Health. Vol.12, No.2 (2007), 195-200|
|Abstract:||Background: Artemether-lumefantrine (AL) is the only fixed, artemisinin-based combination antimalarial drug which is registered internationally and deployed on a large scale. Absorption of the hydrophobic lipophilic lumefantrine component varies widely between individuals and is greatly increased by fat coadministration; but patients with acute malaria are frequently nauseated and anorexic, making dietary advice difficult to comply with. The aim of this study was to describe the dose-response relationship between coadministration of fat and relative lumefantrine bioavailability, in order to determine the minimum amount of fat necessary to optimize absorption. Method: We conducted a multiple crossover pharmacokinetic study in 12 healthy volunteers. This compared the area under the plasma concentration-time curve (AUC) for lumefantrine after administration of a single dose of AL in the fasting state given with 0, 10, 40, 150 and 500 ml of soya milk corresponding to 0, 0.32, 1.28, 4.8 and 16 g of fat. All volumes of milk supplements were tested in all subjects with a 3- to 4-week washout period in-between. Results: A dose-response relationship was demonstrated between the volume of soya milk administered and lumefantrine bioavailability. AL administration with soya milk increased the lumefantrine AUC more than five fold. The population mean estimated volume of soya milk required to obtain 90% of maximum effect (in terms of lumefantrine AUC) was 36 ml (corresponding to 1.2 g of fat). Conclusions: Coadministration of artemether-lumefantrine with a relatively small amount of fat (as soya milk) was required to ensure maximum absorption of lumefantrine in healthy adult volunteers. © 2007 Blackwell Publishing Ltd.|
|Appears in Collections:||Scopus 2006-2010|
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