Monday, September 25
Presented by BioreclamationIVT
In vitro Prediction of Drug Metabolism and Transport Using Primary Human Hepatocytes
This lecture will provide researchers information on how human hepatocytes are uniquely capable of answering important ADME questions in the most accurate and predictive manner. It will highlight human primary hepatocytes as a physiologically relevant in vitro model for investigation of drug metabolism and transport.
Lack of metabolic competence is a major limitation for the majority of current cell-based assays used for evaluation of drug efficacy and toxicity. Many promising medications identified using these methods have failed in clinical trials due to either unexpected human toxicity or lack of efficacy. Properly cultured human primary hepatocytes (HPH) retaining physiologically relevant expression and function of major drug-metabolizing enzymes and transporters have been well-accepted as in vitro models for testing drug metabolism and transport. Our presentation will describe the molecular basis of metabolism-mediated conversion of PK11195 from an antagonist to an agonist of the constitutive androstane receptor in HPH. Utilizing metformin as a model compound, we will also provide experimental evidence to show that repression of BSEP expression in HPH may contribute to clinically observed drug-induced cholestasis.
The BioreclamationIVT sponsored symposium will focus on in vitro application of HPH models for ADME assays to provide the attendees with a better understanding of metabolism-mediated pharmacodynamics changes of drug actions, as well as the role of BSEP repression in drug-induced cholestasis. The presentation is intended to stimulate awareness of the importance of metabolic capacity in in vitro cell-based drug evaluation.