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

Back, Hyun-moon (författare)
Chungnam Natl Univ, Coll Pharm, 99 Daehak Ro, Daejeon 34134, South Korea.
Song, Byungjeong (författare)
JW Pharmaceut, Drug Discovery Ctr, Seoul 06725, South Korea.
Pradhan, Sudeep (författare)
Univ Otago, Sch Pharm, Dunedin 9054, New Zealand.
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Chae, Jung-woo (författare)
Chungnam Natl Univ, Coll Pharm, 99 Daehak Ro, Daejeon 34134, South Korea.
Han, Nayoung (författare)
Seoul Natl Univ, Coll Pharm, Seoul 03080, South Korea.
Kang, Wonku (författare)
Chung Ang Univ, Coll Pharm, Seoul 06974, South Korea.
Chang, Min Jung (författare)
Yonsei Univ, Coll Pharm, Incheon 21983, South Korea.;Yonsei Univ, Yonsei Inst Pharmaceut Sci, Incheon 21983, South Korea.;Yonsei Univ, Coll Med & Pharm, Dept Pharmaceut Med & Regulatory Sci, Incheon 21983, South Korea.
Zheng, Jiao (författare)
Fudan Univ, Huashan Hosp, Dept Pharm, Shanghai 200040, Peoples R China.
Kwon, Kwang-il (författare)
Chungnam Natl Univ, Coll Pharm, 99 Daehak Ro, Daejeon 34134, South Korea.
Karlsson, Mats O (författare)
Uppsala universitet,Institutionen för farmaceutisk biovetenskap
Yun, Hwi-yeol (författare)
Chungnam Natl Univ, Coll Pharm, 99 Daehak Ro, Daejeon 34134, South Korea.
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Chungnam Natl Univ, Coll Pharm, 99 Daehak Ro, Daejeon 34134, South Korea JW Pharmaceut, Drug Discovery Ctr, Seoul 06725, South Korea. (creator_code:org_t)
2018-01-25
2018
Engelska.
Ingår i: BMC Pharmacology & Toxicology. - : BIOMED CENTRAL LTD. - 2050-6511. ; 19
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

Nyckelord

Food effect
Gastrointestinal system
Fenofibrate
NONMEM
Drug absorption

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