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A mechanism-based pharmacokinetic model of fenofibrate for explaining increased drug absorption after food consumption
Chungnam Natl Univ, Coll Pharm, 99 Daehak Ro, Daejeon 34134, South Korea..
JW Pharmaceut, Drug Discovery Ctr, Seoul 06725, South Korea..
Univ Otago, Sch Pharm, Dunedin 9054, New Zealand..
Chungnam Natl Univ, Coll Pharm, 99 Daehak Ro, Daejeon 34134, South Korea..
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2018 (English)In: BMC Pharmacology & Toxicology, E-ISSN 2050-6511, Vol. 19, article id 4Article in journal (Refereed) Published
Abstract [en]

Background: Oral administration of drugs is convenient and shows good compliance but it can be affected by many factors in the gastrointestinal (GI) system. Consumption of food is one of the major factors affecting the GI system and consequently the absorption of drugs. The aim of this study was to develop a mechanistic GI absorption model for explaining the effect of food on fenofibrate pharmacokinetics (PK), focusing on the food type and calorie content.

Methods: Clinical data from a fenofibrate PK study involving three different conditions (fasting, standard meals and high-fat meals) were used. The model was developed by nonlinear mixed effect modeling method. Both linear and nonlinear effects were evaluated to explain the impact of food intake on drug absorption. Similarly, to explain changes in gastric emptying time for the drug due to food effects was evaluated.

Results: The gastric emptying rate increased by 61.7% during the first 6.94 h after food consumption. Increased calories in the duodenum increased the absorption rate constant of the drug in fed conditions (standard meal = 16.5%, high-fat meal = 21.8%) compared with fasted condition. The final model displayed good prediction power and precision.

Conclusions: A mechanistic GI absorption model for quantitatively evaluating the effects of food on fenofibrate absorption was successfully developed, and acceptable parameters were obtained. The mechanism-based PK model of fenofibrate can quantify the effects of food on drug absorption by food type and calorie content.

Place, publisher, year, edition, pages
BIOMED CENTRAL LTD , 2018. Vol. 19, article id 4
Keywords [en]
Food effect, Gastrointestinal system, Fenofibrate, NONMEM, Drug absorption
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:uu:diva-346230DOI: 10.1186/s40360-018-0194-5ISI: 000423664900001PubMedID: 29370865OAI: oai:DiVA.org:uu-346230DiVA, id: diva2:1191477
Note

De två sista författarna delar på sistaförfattarskapet.

Available from: 2018-03-19 Created: 2018-03-19 Last updated: 2018-03-19Bibliographically approved

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Karlsson, Mats O

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