Evaluation of BCRP-Related DDIs Between Methotrexate and Cyclosporin A Using Physiologically Based Pharmacokinetic Modelling.

ABSTRACT:

Background and objective

This study provides a physiologically based pharmacokinetic (PBPK) model-based analysis of the potential drug-drug interaction (DDI) between cyclosporin A (CsA), a breast cancer resistance protein transporter (BCRP) inhibitor, and methotrexate (MTX), a putative BCRP substrate.

Methods

PBPK models for CsA and MTX were built using open-source tools and published data for both model building and for model verification and validation. The MTX and CsA PBPK models were evaluated for their application in simulating BCRP-related DDIs. A qualification of an introduced empirical uniform in vitro scaling factor of K_i values for transporter inhibition by CsA was conducted by using a previously developed model of rosuvastatin (sensitive index BCRP subs

SUBMITTER: Schaller S 

PROVIDER: S-EPMC12011704 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature