Generic placeholder image

Current Topics in Medicinal Chemistry


ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

In Vitro Human Hepatocyte-Based Experimental Systems for the Evaluation of Human Drug Metabolism, Drug-Drug Interactions, and Drug Toxicity in Drug Development

Author(s): Albert P. Li

Volume 14, Issue 11, 2014

Page: [1325 - 1338] Pages: 14

DOI: 10.2174/1568026614666140506114411

Price: $65


Species difference in drug metabolism and drug toxicity is a well-established phenomenon. As a result, the classical paradigm of preclinical testing of drug candidates in animals may not be appropriate. One preclinical approach to evaluate human drug properties, especially ADMET (absorption, disposition, metabolism, elimination, and toxicity) properties, is to apply in vitro experimental systems with relevant human properties. The latest advances include the use of human hepatocytes to evaluate hepatic uptake, metabolism, efflux and toxicity. Successful cryopreservation of human hepatocytes to retain high viability, metabolic capacity, as well as the ability to be cultured allow routine application of this relevant experimental system. This review summarizes the latest findings on human hepatocytes isolation, cryopreservation, culturing, as well as application in the evaluation of metabolic stability, metabolite profiling, hepatic uptake and efflux, metabolic drug-drug interactions, and drug toxicity. The use of hepatocyte to evaluate the role of metabolism in drug toxicity represents a major advance in drug toxicity evaluation. The use of the novel integrated discrete multiple organ coculture (IdMOC) system allows the evaluation of the role of hepatic metabolism on nonhepatic toxicity.

Keywords: Cryopreserved hepatocytes, drug development, drug discovery, drug-drug interactions, drug metabolism, drug toxicity, human hepatocytes, in vitro assays, IdMOC.

Graphical Abstract

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy