Measurement of human intrinsic hepatic clearance

Method Description

This in vitro method is used to determine human intrinsic hepatic clearance by measuring substrate depletion over time in suspensions of pooled cryopreserved primary human hepatocytes. Test chemicals are incubated with hepatocytes at a single concentration, and the decrease in parent compound concentration is quantified analytically. The method provides direct quantitative information on hepatic metabolic capacity and is a key input for in vitro–to–in vivo extrapolation (IVIVE) and toxicokinetic modelling.

This method was selected together with the complementary in vitro method for plasma protein binding and a defined approach for toxicokinetic interpretation, as part of a single project submitted to the OECD Test Guidelines Programme.