Physiologically-based pharmacokinetic pharmacodynamic parent-metabolite model of edoxaban to predict drug-drug-disease interactions: M4 contribution.

ABSTRACT: This study aimed to develop a physiologically-based pharmacokinetic pharmacodynamic (PBPK/PD) parent-metabolite model of edoxaban, an oral anticoagulant with a narrow therapeutic index, and to predict pharmacokinetic (PK)/PD profiles and potential drug-drug-disease interactions (DDDIs) in patients with renal impairment. A whole-body PBPK model with a linear additive PD model of edoxaban and its active metabolite M4 was developed and validated in SimCYP for healthy adults with or without interacting drugs. The model was extrapolated to situations including renal impairment and drug-drug interactions (DDIs). Observed PK and PD data in adults were compared with predicted data. The effect of several model parameters on the PK/PD response of edoxaban and M4 was investigated in sensitivity analy

SUBMITTER: Xu R 

PROVIDER: S-EPMC10431043 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature