Summary Report of a FDA/SOT Meeting in USA

Advances in the technology of human cell and tissue culture and the increasing availability of human materials for laboratory studies have made the use of in vitro human models in metabolism, transport, toxicology and pharmacodynamics studies much increased, and the obtained results can be used for quantitative modeling of pharmacokinetic behavior and estimating in vivo drug-drug interactions, pharmacological effects and/or toxicities. Bearing in mind the usefulness of such in vitro models in toxicological risk assessment, a workshop was held by the Society of Toxicology to evaluate the current status of in vitro human models and to make common recommendations on the use of such models especially to develop the PK basis risk assessment. This report summarizes the evaluation and recommendations on the application and improvement of in vitro models using human tissues, cells or subcellular fractions together with physiologically based pharmacokinetic (PBPK) modeling for quantitatively predicting human metabolism, potential drug-drug interactions and pharmaco-toxicodynamic behavior.