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Updated: Apr 19, 2026

Author Spotlight: Developing a Simple and Robust Hepatic Model for Pharmacological and Toxicological Applications
Published on: October 20, 2023
Practical permeability-based hepatic clearance classification system (HepCCS) in drug discovery
Peter W Fan1, Yang Song, Leonid M Berezhkovskiy
1Department of Drug Metabolism & Pharmacokinetics, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Background:
The use of liver microsomes and hepatocytes to predict total in vivo clearance is standard practice in the pharmaceutical industry; however, metabolic stability data alone cannot always predict in vivo clearance accurately.
Results:
Apparent permeability generated from Mardin-Darby canine kidney cells and rat hepatocyte uptake for 33 discovery compounds were obtained.
Conclusion:
When there is underprediction of in vivo clearance, compounds with low apparent permeability (less than 3 × 10(-6) cm/s) all exhibited hepatic uptake. A systematic approach in the form of a classification system (hepatic clearance classification system) and decision tree that will help drug discovery scientists understand in vitro-in vivo clearance prediction disconnect early is proposed.
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