Potential for pharmacokinetic interactions between Schisandra sphenanthera and bosutinib, but not imatinib: in vitro metabolism study combined with a physiologically-based pharmacokinetic modelling approach.

ABSTRACT:

Aims

This study aimed to investigate the potential interaction between Schisandra sphenanthera, imatinib and bosutinib combining in vitro and in silico methods.

Methods

In vitro metabolism of imatinib and bosutinib using recombinant enzymes and human liver microsomes were investigated in the presence and absence of Schisandra lignans. Physiologically-based pharmacokinetic (PBPK) models for the lignans accounting for reversible and mechanism-based inhibitions and induction of CYP3A enzymes were built in the Simcyp Simulator (version 17) and evaluated for their capability to predict interactions with midazolam and tacrolimus. Their potential effect on systemic exposures of imatinib and bosutinib were predicted using PBPK in silico simulations.

Results

Schisantherin A an

SUBMITTER: Adiwidjaja J 

PROVIDER: S-EPMC7495297 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature