Primary hepatocytes as a model to analyze species-specific toxicity and drug metabolism

Abstract

Background: Compound failures have been emerging in later stages of pharmaceutical drug development and are in many cases not detected until the administration to humans in clinical trials or even after approval. Among the most frequent adverse effects are drug-induced liver injury generated by species-specific susceptibilities (e.g., in xenobiotic metabolism and/or the occurrence of idiosyncratic drug hepatotoxicity). Objectives: Detecting or predicting unfavorable drug effects on the liver as early as possible in drug development is crucial in making the drug development process more efficient and the application of new drugs to humans in clinical studies and medical use safer. Methods: To achieve this goal, primary hepatocyte cultures from various species, including humans, are analyzed for morphological, functional and gene expression alterations after compound treatment. Results/conclusion: Primary hepatocyte cultures appear to be a promising tool for the detection of general or liver toxicity and the evaluation of species-specific drug effects.

Keywords::

• cell culture
• drug development
• drug-induced liver injury
• hepatotoxicity
• idiosyncrasy
• in vitro model
• primary hepatocytes
• xenobiotic metabolism

Acknowledgements

We are grateful to L Richert (KaLy-Cell, France) for the supply of human hepatocytes.

Notes