Prediction of drug-drug interactions between roflumilast and CYP3A4/1A2 perpetrators using a physiologically-based pharmacokinetic (PBPK) approach.

ABSTRACT: This study aimed to develop a physiologically-based pharmacokinetic (PBPK) model to predict changes in the pharmacokinetics (PK) and pharmacodynamics (PD, PDE4 inhibition) of roflumilast (ROF) and ROF N-oxide when co-administered with eight CYP3A4/1A2 perpetrators. The population PBPK model of ROF and ROF N-oxide has been successfully developed and validated based on the four clinical PK studies and five clinical drug-drug interactions (DDIs) studies. In PK simulations, every ratio of prediction to observation for PK parameters fell within the range 0.7 to 1.5. In DDI simulations, except for tow peak concentration ratios (C_max) of ROF with rifampicin (prediction: 0.63 vs. observation: 0.19) and with cimetidine (prediction: 1.07 vs. observation: 1.85), the remaining predicted rat

SUBMITTER: Jia G 

PROVIDER: S-EPMC10762902 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature