Title: Drug-induced hepatotoxicity: Mechanisms and predictive methodologies

Date: Saturday, 27th November 2010

Time: 14:15 GMT

The liver is the principal organ that is capable of converting drugs into metabolites that can be readily eliminated from the body. As such, the liver "sees" a higher drug load than many other organs in the body. Drug-induced liver injury (DILI) is one of the most common adverse events causing drug non-approvals and post-launch drug withdrawals.

The mechanisms by which drugs damage the liver are variable, complex, and often poorly understood. This is especially the case when damage only occurs rarely and only in susceptible people (i.e., idiosyncratic liver injury). Recent emerging studies have pointed to the importance of several key mechanisms that can lead to clinical manifestation of DILI. These mechanisms include oxidative stress, mitochondrial health, reactive metabolite formation and bile acid damage. In vitro assays and in vivo animal models to study these damage mechanisms are now available.

The focus of this presentation will be in vitro assays and predictive methodologies to minimize DILI by new chemical entities (NCEs). Case studies to demonstrate the utilities of these assay methodologies and predictive algorithms will be presented.