PBPK coupled systems biology modeling for mechanistic predictions of metabolic pathways interactions
Résumé
A major challenge for drug development and chemical safety assessment in general is the prediction of pharmacokinetic and pharmacodynamic interactions between drugs, natural chemicals or environmental contaminants. Computational modeling of ADME processes is theoretically able to describe metabolic interactions in realistic mixtures of tens to hundreds of substances. This lecture will briefly review the past developments in the area of physiologically-based pharmacokinetic (PBPK) modelling of interactions. I will also present recent approaches to the question, and the capabilities of new software tools to facilitate that development. A systems biology approach to large-scale prediction of metabolic interactions is advantageous on several counts and technically feasible. However, ways to obtain the required parameters need to be further explored.