ArticleEuropean journal of drug metabolism and pharmacokinetics2019
A Gallbladder-Based Enterohepatic Circulation Model for Pharmacokinetic Studies.
Article in European journal of drug metabolism and pharmacokinetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Physiologically Based Pharmacokinetic Modeling to Predict Drug-Drug Interactions of Soticlestat as a Victim of CYP Induction and Inhibition, and as a Perpetrator of CYP and P-Glycoprotein Inhibition.Clinical pharmacology in drug development · 2025Article
- Pharmacokinetic Simulation and Area under the Curve Estimation of Drugs Subject to Enterohepatic Circulation.Pharmaceutics · 2024Article
- Enteric reabsorption processes and their impact on drug pharmacokinetics.Scientific reports · 2021Article
- Population pharmacokinetics of regorafenib in solid tumours: Exposure in clinical practice considering enterohepatic circulation and food intake.British journal of clinical pharmacology · 2020Article
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2 authors.
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Abstract
BACKGROUND AND
objectivesStrategies for modeling the enterohepatic circulation (EHC) process reported in the literature vary; however, gallbladder-based models currently provide the best physiological representation of the process. Regardless, the addition of a gallbladder to the model does not fully depict the physiology of EHC. A more physiological gallbladder-based EHC model is needed. This model should take into account a physiological representation of the bile secretion, gallbladder filling and emptying, the duration of gallbladder emptying, and irregular mealtimes. Considering all of these factors, the objectives of the present analysis were to propose a gallbladder-based EHC model and then to use that model to perform sensitivity analyses evaluating the effect of the extent of EHC on the pharmacokinetic profile and noncompartmental analysis (NCA) calculations.
methodsA gallbladder-based model that describes the EHC process was developed and used to perform determinant simulations assuming various degrees of EHC. Next, these simulations were compared to evaluate the effect of the EHC on the pharmacokinetic profiles of orally administered drugs. The influence of the EHC process on the NCA calculations was determined while assuming two sampling schemes that differed in the times at which sampling was performed in relation to meal times.
resultsThe presence of EHC results in nonlinearity in the system and changes the pharmacokinetic profile, affecting the maximum concentration (C
conclusionCaution should be taken when designing clinical studies for drugs that undergo EHC. It may be essential to consider the timing of meals when planning pharmacokinetic studies and defining sampling times. The period over which samples are taken needs to be extended as compared to that traditionally used with other drugs. Future studies that attempt to identify the best sampling strategies in the presence of EHC are needed.
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