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Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Pharmacometabolomics Informs About Pharmacokinetic Profile of Methylphenidate

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Mechanism-Based Modeling of Gastric Emptying Rate and Gallbladder Emptying in Response to Caloric Intake

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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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.

OriginalsprogEngelsk
TidsskriftCPT: pharmacometrics & systems pharmacology
Vol/bind7
Udgave nummer9
Sider (fra-til)603-612
Antal sider9
ISSN2163-8306
DOI
StatusUdgivet - sep. 2018

ID: 54963935