[Dynamic Simulation of Drug-Drug Interactions by Using Multi-level Physiological Modeling & Simulation Platforms].

　Drug-drug interactions mediated by drug metabolizing enzymes are serious, clinically relevant issues. Prediction and evaluation of the probability and consequences of drug-drug interactions are essential during drug development, as well as during clinical application. A physiologically based pharmacokinetic (PBPK) model, which considers the hierarchical structure of the physiological behavior of drugs, has been demonstrated to be effective for in vitro-in vivo extrapolation of the phenomena of drug-drug interaction (DDI). While commercial software that implements PBPK models is now available, increasing attention has been given to developing similar models on open platforms for systems biology modeling and simulation. Open simulation model development environments, including CellDesigner and PhysioDesigner, have been developed and improved with the advent of research fields associated with systems biology or synthetic biology. Model developers implement their models using the platform, then publish the models in public databases. Through sharing and reuse among researchers, these models can become more generalized and sophisticated. This review article aims to discuss the attractive features and potential of these open platforms, and to evaluate the prediction effectiveness for enzyme induction-based drug-drug interactions via integrating the PBPK models of inducers and substrates and the dynamic models of enzyme induction kinetics.