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A mechanism-based pharmacokinetic model of fenofibrate for explaining increased drug absorption after food consumption

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dc.contributor.authorBack, Hyun-moon-
dc.contributor.authorSong, Byungjeong-
dc.contributor.authorPradhan, Sudeep-
dc.contributor.authorChae, Jung-woo-
dc.contributor.authorHan, Nayoung-
dc.contributor.authorKang, Wonku-
dc.contributor.authorChang, Min Jung-
dc.contributor.authorZheng, Jiao-
dc.contributor.authorKwon, Kwang-il-
dc.contributor.authorKarlsson, Mats O.-
dc.contributor.authorYun, Hwi-yeol-
dc.date.accessioned2018-01-29T05:20:35Z-
dc.date.available2018-01-29T14:22:18Z-
dc.date.issued2018-01-25-
dc.identifier.citationBMC Pharmacology and Toxicology, 25;19(1):4ko_KR
dc.identifier.issn2050-6511-
dc.identifier.urihttps://hdl.handle.net/10371/139312-
dc.description.abstractBackground
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.
ko_KR
dc.description.sponsorshipThis research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT & Future Planning (Grant number 2009–0093815 and 2014R1A1A1006006) and supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant number: HI17C0927). This work was also supported by research funds from Chungnam National Universityko_KR
dc.language.isoenko_KR
dc.publisherBioMed Centralko_KR
dc.subjectFood effectko_KR
dc.subjectGastrointestinal systemko_KR
dc.subjectFenofibrateko_KR
dc.subjectNONMEMko_KR
dc.subjectDrug absorptionko_KR
dc.titleA mechanism-based pharmacokinetic model of fenofibrate for explaining increased drug absorption after food consumptionko_KR
dc.typeArticleko_KR
dc.contributor.AlternativeAuthor백현문-
dc.contributor.AlternativeAuthor송병정-
dc.contributor.AlternativeAuthor채정우-
dc.contributor.AlternativeAuthor한나영-
dc.contributor.AlternativeAuthor강원구-
dc.contributor.AlternativeAuthor장민정-
dc.contributor.AlternativeAuthor윤휘열-
dc.identifier.doi10.1186/s40360-018-0194-5-
dc.language.rfc3066en-
dc.rights.holderThe Author(s).-
dc.date.updated2018-01-28T09:51:21Z-
Appears in Collections:
College of Pharmacy (약학대학)Dept. of Pharmacy (약학과)Journal Papers (저널논문_약학과)
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