Whole-body PBPK model of verapamil and norverapamil as CYP3A4 and P-gp perpetrator drug
This repository contains:
- a PK-Sim snapshot (*.json) file of the current PBPK model
- static content (e.g. text blocks, *.md files) as inputs for an evaluation plan
- an evaluation plan (evaluation-plan.json) to create an evaluation report using the snapshot and static text blocks to display the performance of the model
The latest release of the snapshot of the model, the evaluation plan and the static content can be found here.
The latest release of the PK-Sim project model file and the respective evaluation report can be found here.
This whole-body verapamil PBPK model comprises verapamil R- and S-enantiomers and their main metabolites R- and S-norverapamil. The processes implemented to describe the pharmacokinetics of verapamil and norverapamil include enantioselective plasma protein binding, enantioselective metabolism by CYP3A4, non-stereospecific Pgp transport, and passive glomerular filtration. This verapamil model includes mechanism-based inactivation of CYP3A4 and non-competitive inhibition of Pgp by the verapamil and norverapamil enantiomers and is intended to be used as perpetrator drug in CYP3A4-mediated and P-gp-mediated drug-drug interactions (DDI). The verapamil PBPK model has been developed using data from 45 clinical studies. Model development and application has been published by Hanke et al. 2020 [1].
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The model code is distributed under the GPLv2 License.