Drug-Drug Interaction Between Oxycodone and Diazepam by a Combined in Silico Pharmacokinetic and Pharmacodynamic Modeling Approach.

ABSTRACT: Opioids and benzodiazepines have complex drug-drug interactions (DDIs), which serve as an important source of adverse drug effects. In this work, we predicted the DDI between oxycodone (OXY) and diazepam (DZP) in the human body by applying in silico pharmacokinetic (PK) and pharmacodynamic (PD) modeling and simulation. First, we studied the PK interaction between OXY and DZP with a physiologically based pharmacokinetic (PBPK) model. Second, we applied molecular modeling techniques including molecular docking, molecular dynamics (MD) simulation, and the molecular mechanics/Poisson-Boltzmann surface area (MM-PBSA) free energy method to predict the PD-DDI between these two drugs. The PK interaction between OXY and DZP predicted by the PBPK model was not obvious. No significant interact

SUBMITTER: Ji B 

PROVIDER: S-EPMC8374491 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature