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ADMET and DMPK, Vol. 3. No. 1., 2015.

Review article

https://doi.org/10.5599/admet.3.1.144

The extended clearance model and its use for the interpretation of hepatobiliary elimination data

Gian Camenisch ; Division of Drug Metabolism and Pharmacokinetics, Integrated Drug Disposition Section, No vartis Institutes for BioMedical Research, CH - 4056 Basel, Switzerland
Julia Riede ; Division of Drug Metabolism and Pharmacokinetics, Integrated Drug Disposition Section, No vartis Institutes for BioMedical Research, CH - 4056 Basel, Switzerland
Annett Kunze ; Division of Drug Metabolism and Pharmacokinetics, Integrated Drug Disposition Section, No vartis Institutes for BioMedical Research, CH - 4056 Basel, Switzerland
Jörg Huwyler ; Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, CH - 4056 Basel, Switzerland
Birk Poller ; Division of Drug Metabolism and Pharmacokinetics, Integrated Drug Disposition Section, No vartis Institutes for BioMedical Research, CH - 4056 Basel, Switzerland
Kenichi Umehara ; Division of Drug Metabolism and Pharmacokinetics, Integrated Drug Disposition Section, No vartis Institutes for BioMedical Research, CH - 4056 Basel, Switzerland

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Abstract

Hepatic elimination is a function of the interplay between different processes such as sinusoidal uptake, intracellular metabolism, canalicular (biliary) secretion, and sinusoidal efflux. In this review, we outline how drugs can be classified according to their in vitro determined clearance mechanisms using the extended clearance model as a reference. The approach enables the determination of the rate-determining hepatic clearance step. Some successful applications will be highlighted, together with a discussion on the major consequences for the pharmacokinetics and the drug-drug interaction potential of drugs. Special emphasize is put on the role of passive permeability and active transport processes in hepatic elimination.

Keywords

extended clearance concept classification system; hepatic elimination; passive permeability; transporters

Hrčak ID:

137560

URI

https://hrcak.srce.hr/137560

Publication date:

31.3.2015.

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