Modeling Enterohepatic Circulation
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Purpose of Review
The objective of the current analysis is to review the anatomy and physiology of the enterohepatic circulation (EHC); describe how those intricacies affect drug concentration profiles; present various pharmacokinetic models used in the literature to describe EHC concentration-time data; and provide a categorization of these models based on common features.
The presence of EHC results in longer apparent drug half-lives and the appearance of multiple secondary peaks. Several empirical modeling strategies are present in the literature and these have increased in complexity as our understanding of the impact EHC has on pharmacokinetics, and as the increase in computing power has allowed these models to become more tractable. Although the intent of all these models is to capture the nuances of concentration-time profiles when EHC exists, they remain deficient in their mechanistic representation of the EHC process. In addition, limitations in biological sampling and experimental design present difficulties in our ability to distinguish among some of these models. Finally, the quantitative comparison of different models to literature examples is not possible. Nonetheless, our knowledge of the EHC process and the limitations of our models can be used to inform our interpretation of pharmacokinetic results presented in the literature.
Modeling strategies of EHC vary in the literature. This review article provides a basic review of the EHC process, relates those models to the EHC process, and presents a categorization and summary of modeling strategies implemented to represent EHC.
KeywordsEnterohepatic Circulation Biliary Pharmacokinetic Modeling
Compliance with Ethical Standards
Conflict of Interest
On behalf of all authors, the corresponding author states that there is no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
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