Isolated hepatocytes or their enzymes comprise the basis of most in vitro DMPK and toxicity assays used to predict human hepatic outcomes. Because hepato-specific functions are typically lost in the first hours or days of culture in many in vitro hepatic models, such models are of limited use in instances where meaningfully predictive simulation of a compound’s properties require that the in vitro model maintain such function stably over longer time periods, such as where compounds clear slowly, where metabolites are generated over extended periods of time, where membrane polarization is required for biliary canalicular formation, or where cellular conditions may cumulate after repeated dosing, such as in cholestatic toxicities. To address this limitation, more advanced liver models have been developed and extensively characterized. These long-term models have been shown to more accurately predict intrinsic clearance, metabolite generation, and toxicity profiles.
1. Learn about advanced liver models for improved in vitro prediction.
2. Learn about the next wave of organ-on-chip with microfluidic advancements.