In vitro investigation of the role of cyp dependent metabolism in drug hepatotoxicity using the THLE-CYP cell panel

摘要

Drug-induced liver injury (DILI) is a major cause of drug toxicity and drug withdrawal and is a major obstacle in the development of new medicines (Antoine et al., 2008). It is therefore important to identify new approaches for early deselection of compounds that can cause DILI in man and also to develop an improved understanding of underlying mechanisms. One promising in vitro model is a panel of SV40 T-antigen-immortalized human liver epithelial (THLE) cells which express individual CYP isoforms driven by a Cytomegalovirus (CMV) promoter (Mace et al., 1997). We have used this cell approach to evaluate toxicity of 34 marketed drugs reported to cause severe/marked or no DILI in man, and to explore the role played by individual CYP isoforms in cell toxicity.