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Model-Based Prediction of Plasma Concentration and Enterohepatic Circulation of Total Bile Acids in Humans

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@article{60172ca3d59848a297d3fe09b0d80558,
title = "Model-Based Prediction of Plasma Concentration and Enterohepatic Circulation of Total Bile Acids in Humans",
abstract = "Bile acids released postprandially can modify the rate and extent of lipophilic compounds' absorption. This study aimed to predict the enterohepatic circulation (EHC) of total bile acids (TBAs) in response to caloric intake from their spillover in plasma. A model for TBA EHC was combined with a previously developed gastric emptying (GE) model. Longitudinal gallbladder volumes and TBA plasma concentration data from 30 subjects studied after ingestion of four different test drinks were supplemented with literature data. Postprandial gallbladder refilling periods were implemented to improve model predictions. The TBA hepatic extraction was reduced with the high-fat drink. Basal and nutrient-induced gallbladder emptying rates were altered by type 2 diabetes (T2D). The model was predictive of the central trend and the variability of gallbladder volume and TBA plasma concentration for all test drinks. Integration of this model within physiological pharmacokinetic modeling frameworks could improve the predictions for lipophilic compounds' absorption considerably.",
author = "Benjamin Guiastrennec and Sonne, {David P} and Martin Bergstrand and Tina Vilsb{\o}ll and Knop, {Filip K} and Karlsson, {Mats O}",
note = "{\textcopyright} 2018 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.",
year = "2018",
month = sep,
doi = "10.1002/psp4.12325",
language = "English",
volume = "7",
pages = "603--612",
journal = "CPT: Pharmacometrics and Systems Pharmacology",
issn = "2163-8306",
publisher = "Nature Publishing Group",
number = "9",

}

RIS

TY - JOUR

T1 - Model-Based Prediction of Plasma Concentration and Enterohepatic Circulation of Total Bile Acids in Humans

AU - Guiastrennec, Benjamin

AU - Sonne, David P

AU - Bergstrand, Martin

AU - Vilsbøll, Tina

AU - Knop, Filip K

AU - Karlsson, Mats O

N1 - © 2018 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.

PY - 2018/9

Y1 - 2018/9

N2 - Bile acids released postprandially can modify the rate and extent of lipophilic compounds' absorption. This study aimed to predict the enterohepatic circulation (EHC) of total bile acids (TBAs) in response to caloric intake from their spillover in plasma. A model for TBA EHC was combined with a previously developed gastric emptying (GE) model. Longitudinal gallbladder volumes and TBA plasma concentration data from 30 subjects studied after ingestion of four different test drinks were supplemented with literature data. Postprandial gallbladder refilling periods were implemented to improve model predictions. The TBA hepatic extraction was reduced with the high-fat drink. Basal and nutrient-induced gallbladder emptying rates were altered by type 2 diabetes (T2D). The model was predictive of the central trend and the variability of gallbladder volume and TBA plasma concentration for all test drinks. Integration of this model within physiological pharmacokinetic modeling frameworks could improve the predictions for lipophilic compounds' absorption considerably.

AB - Bile acids released postprandially can modify the rate and extent of lipophilic compounds' absorption. This study aimed to predict the enterohepatic circulation (EHC) of total bile acids (TBAs) in response to caloric intake from their spillover in plasma. A model for TBA EHC was combined with a previously developed gastric emptying (GE) model. Longitudinal gallbladder volumes and TBA plasma concentration data from 30 subjects studied after ingestion of four different test drinks were supplemented with literature data. Postprandial gallbladder refilling periods were implemented to improve model predictions. The TBA hepatic extraction was reduced with the high-fat drink. Basal and nutrient-induced gallbladder emptying rates were altered by type 2 diabetes (T2D). The model was predictive of the central trend and the variability of gallbladder volume and TBA plasma concentration for all test drinks. Integration of this model within physiological pharmacokinetic modeling frameworks could improve the predictions for lipophilic compounds' absorption considerably.

U2 - 10.1002/psp4.12325

DO - 10.1002/psp4.12325

M3 - Journal article

C2 - 30070437

VL - 7

SP - 603

EP - 612

JO - CPT: Pharmacometrics and Systems Pharmacology

JF - CPT: Pharmacometrics and Systems Pharmacology

SN - 2163-8306

IS - 9

ER -

ID: 54963935