Prediction of Drug-Drug Interactions Between Opioids and Overdosed Benzodiazepines Using Physiologically Based Pharmacokinetic (PBPK) Modeling and Simulation.

Our results appear to indicate that pharmacodynamics may play a more important role than PKs in causing DDIs between opioids and benzodiazepines. This study also demonstrated that molecular modeling can be a very useful tool to mitigate the problem of "missing metabolic reaction parameters" in PK modeling and simulation.