A Comprehensive Overview of the Current Status and Application of Predictive ADMET: Introduction and Overview

Pharmaco- and toxicokinetics, that is, the assessment of adsorption, distribution, metabolism, and excretion of xenobiotics, have transformed our understanding of in vivo pharmacology and toxicology. Astonishingly, some areas of regulatory toxicology still do not request such information, which can boost our understanding of the human relevance of our findings. The respective models of substance kinetics, such as physiology-based pharmacokinetic models, are increasingly refined by the input from in vitro models, for example, for epithelial barrier function or metabolism of test agents. In vitro, kinetic phenomena play a similar role, that is, how the test agent is ultimately available to the cells as similar redistributions and transformations occur, but this is regularly neglected in our interpretations of results. Reverse biokinetics, that is, a quantitative in vitro-to-in vivo extrapolation, is critically important to predict in vivo exposures corresponding to active concentrations on a cell and tissue level, thus making predictive use of in vitro findings. This information represents the complement to hazard identification and characterization by cellular models in order to develop a systems toxicology approach.