Suspension Hepatocyte Metabolism Incubation Tips and Best Practices

Data obtained during in vitro investigation of test compounds is essential for effective extrapolation of in vivo ADMET/DMPK characteristics. Primary hepatocyte incubations are still considered the gold standard for in vitro assessment of a compound due to their ability to provide superior in vivo stability and clearance predictions. These in vitro studies can provide key information to help guide researchers towards safe dosing parameters for subsequent in vivo testing.
Generally, these types of incubations are carried out using pooled cryopreserved primary hepatocytes in suspension cultures. These assays can generate a diverse data set which can be used to determine:
• Prediction of the intrinsic clearance of compounds
• Number of metabolites formed
• Reactive and/or toxic metabolite formation
• Inhibition of endogenous metabolic enzymes
• Which small animal model might be the most representative for toxicology studies prior to first-in-human studies.
While the experimental design of these assays might appear straight forward, scientists that are unfamiliar with these studies may not realize how difficult working with cryopreserved primary hepatocytes can be. Over the years, the steps, details, and procedures necessary for a successful in vitro study have been honed though research and trial and error. Understanding the proper procedures and details involved with these types of studies can greatly increase the quality and reproducibility of the data generated by these assays.
For more useful information on utilizing hepatocytes, visit: bioivt.com/resources/educatio...