Enterohepatic circulation - Physiological, pharmacokinetic and clinical implications

Roberts, M. S., Magnusson, B. M., Burczynski, F. J. and Weiss, M. (2002) Enterohepatic circulation - Physiological, pharmacokinetic and clinical implications. Clinical Pharmacokinetics, 41 10: 751-790. doi:10.2165/00003088-200241100-00005

Author Roberts, M. S.
Magnusson, B. M.
Burczynski, F. J.
Weiss, M.
Title Enterohepatic circulation - Physiological, pharmacokinetic and clinical implications
Journal name Clinical Pharmacokinetics   Check publisher's open access policy
ISSN 0312-5963
Publication date 2002-01-01
Year available 2002
Sub-type Critical review of research, literature review, critical commentary
DOI 10.2165/00003088-200241100-00005
Open Access Status Not yet assessed
Volume 41
Issue 10
Start page 751
End page 790
Total pages 40
Editor Nick Holford
Place of publication New Zealand
Publisher Adis International Limited
Language eng
Subject C1
320503 Clinical Pharmacology and Therapeutics
730118 Organs, diseases and abnormal conditions not elsewhere classified
Abstract Enterohepatic recycling occurs by biliary excretion and intestinal reabsorption of a solute, sometimes with hepatic conjugation and intestinal deconjugation. Cycling is often associated with multiple peaks and a longer apparent half-life in a plasma concentration-time profile. Factors affecting biliary excretion include drug characteristics (chemical structure, polarity and molecular size), transport across sinusoidal plasma membrane and canniculae membranes, biotransformation and possible reabsorption from intrahepatic bile ductules. Intestinal reabsorption to complete the enterohepatic cycle may depend on hydrolysis of a drug conjugate by gut bacteria. Bioavailability is also affected by the extent of intestinal absorption, gut-wall P-glycoprotein efflux and gut-wall metabolism. Recently, there has been a considerable increase in our understanding of the role of transporters, of gene expression of intestinal and hepatic enzymes, and of hepatic zonation. Drugs, disease and genetics may result in induced or inhibited activity of transporters and metabolising enzymes. Reduced expression of one transporter, for example hepatic canalicular multidrug resistance-associated protein (MRP) 2, is often associated with enhanced expression of others, for example the usually quiescent basolateral efflux MRP3, to limit hepatic toxicity. In addition, physiologically relevant pharmacokinetic models, which describe enterohepatic recirculation in terms of its determinants (such as sporadic gall bladder emptying), have been developed. In general, enterohepatic recirculation may prolong the pharmacological effect of certain drugs and drug metabolites. Of particular importance is the potential amplifying effect of enterohepatic variability in defining differences in the bioavailability, apparent volume of distribution and clearance of a given compound. Genetic abnormalities, disease states, orally administered adsorbents and certain coadministered drugs all affect enterohepatic recycling.
Keyword Pharmacology & Pharmacy
Bile-acid Uptake
Taurocholate Cotransporting Polypeptide
Resistance-associated Protein
Quaternary Ammonium-compounds
Kidney-transplant Recipients
Q-Index Code C1
Institutional Status UQ
Additional Notes This document is a journal review.

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
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Created: Wed, 15 Aug 2007, 03:44:20 EST