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

Hyun moon Back, Byungjeong Song, Sudeep Pradhan, Jung woo Chae, Nayoung Han, Wonku Kang, Min Jung Chang, Jiao Zheng, Kwang il Kwon, Mats O. Karlsson, Hwi yeol Yun

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
Article number4
JournalBMC Pharmacology and Toxicology
Volume19
Issue number1
DOIs
Publication statusPublished - 2018 Jan 25

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Fenofibrate
Pharmacokinetics
Food
Pharmaceutical Preparations
Meals
Gastric Emptying
Fats
Duodenum
Oral Administration
Fasting
Eating

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Cite this

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. / A mechanism-based pharmacokinetic model of fenofibrate for explaining increased drug absorption after food consumption. In: BMC Pharmacology and Toxicology. 2018 ; Vol. 19, No. 1.
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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.",
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A mechanism-based pharmacokinetic model of fenofibrate for explaining increased drug absorption after food consumption. / 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.

In: BMC Pharmacology and Toxicology, Vol. 19, No. 1, 4, 25.01.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A mechanism-based pharmacokinetic model of fenofibrate for explaining increased drug absorption after food consumption

AU - Back, Hyun moon

AU - Song, Byungjeong

AU - Pradhan, Sudeep

AU - Chae, Jung woo

AU - Han, Nayoung

AU - Kang, Wonku

AU - Chang, Min Jung

AU - Zheng, Jiao

AU - Kwon, Kwang il

AU - Karlsson, Mats O.

AU - Yun, Hwi yeol

PY - 2018/1/25

Y1 - 2018/1/25

N2 - 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.

AB - 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.

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