In Vitro Approach to Predictive Toxicokinetics.

The overall objective of this research program is to develop new approaches to predict the systemic toxicokinetics of chemicals utilizing in vitro experimental model systems and biologically-based kinetic (BBK) models. The focus of the proposed research is to test the hypothesis that in vitro measurements of membrane transport parameters in hepatic membrane vesicles are predictive of hepatic transport in vivo. Although this study is focused on transport processes in one particular organ, i.e. hepatic transport processes, these processes are a major controlling factor in determining systemic kinetics of many chemicals, particularly those which do not satisfy the 'perfusion limited' condition usually assumed in many current PBPK models.