S50 The utility of 3D hepatocyte spheroids in addressing modern problems in drug metabolism

Jinping Gan , Pharmaceutical Candidate Optimization, Pharmaceutical Research Institute, Bristol-Myers Squibb, Princeton, NJ
Cultures and suspensions of primary hepatocytes have been used successfully in a variety of ADME-related contexts, including clearance prediction, biotransformation, transporter evaluation, and enzyme induction studies. However, its short lifespan has limited its use in the clearance prediction of low turnover compounds, the recaptulation of complex in vivo biotransformation, and the liver toxicity prediction due to mechanisms which require longer duration of treatment. 3D cultures of hepatocyte such as spheroids are novel models that hold promise to address these challenges. We have developed a in-house spheroid model with primary hepatocytes from multiple species over the last few years. Detailed characterization of the spheroid model will be presented, as well as the application of this model in addressing the aforementioned problems.