SHERP

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

Cited 0 time in webofscience Cited 0 time in scopus
Authors
Back, Hyun-moon; Song, Byungjeong; Pradhan, Sudeep; Chae, Jung-woo; Han, Nayoung; Kang, Wonku; Chang, Min Jung; Zheng, Jiao; Kwon, Kwang-il; Karlsson, Mats O.; Yun, Hwi-yeol
Issue Date
2018-01-25
Publisher
BioMed Central
Citation
BMC Pharmacology and Toxicology, 25;19(1):4
Keywords
Food effectGastrointestinal systemFenofibrateNONMEMDrug absorption
Abstract
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.
ISSN
2050-6511
Language
English
URI
http://hdl.handle.net/10371/139312
DOI
https://doi.org/10.1186/s40360-018-0194-5
Files in This Item:
Appears in Collections:
College of Pharmacy (약학대학)Dept. of Pharmacy (약학과)Journal Papers (저널논문_약학과)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse