Verapamil-Model

Whole-body PBPK model of verapamil as CYP3A4 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 verapamil model is intended to be used as perpetrator drug in CYP3A4-mediated drug-drug interactions (DDI).

This whole-body verapamil PBPK model comprises metabolization by CYP3A4 and CYP2C8. The dose- and time-dependent nonlinear behavior of verapamil is described through implementation of the CYP3A4 mechanism-based (auto-)inactivation by verapamil. The verapamil PBPK model has been developed using in particular published pharmacokinetic clinical data by Barbarash et al. 2010 [1], Johnston et al. 1999 [2] and McAllister et al. 2013 [3].

Code of conduct

Everyone interacting in the Open Systems Pharmacology community (codebases, issue trackers, chat rooms, mailing lists etc...) is expected to follow the Open Systems Pharmacology code of conduct.

Contribution

We encourage contribution to the Open Systems Pharmacology community. Before getting started please read the contribution guidelines. If you are contributing code, please be familiar with the coding standard.

License

The model code is distributed under the GPLv2 License.

References

[1] Barbarash 1988 Barbarash RA, Bauman JL, Fischer JH, Kondos GT, Batenhorst RL. Near-total reduction in verapamil bioavailability by rifampin. Electrocardiographic correlates. Chest. 1988 Nov;94(5):954-9. PubMed PMID: 3180898.

[2] Johnston 1981 Johnston A, Burgess CD, Hamer J. Systemic availability of oral verapamil and effect on PR interval in man. Br J Clin Pharmacol. 1981 Sep;12(3):397-400. PubMed PMID: 7295469; PubMed Central PMCID: PMC1401793.

[3] McAllister 1982 McAllister RG Jr, Kirsten EB. The pharmacology of verapamil. IV. Kinetic and dynamic effects after single intravenous and oral doses. Clin Pharmacol Ther. 1982 Apr;31(4):418-26. PubMed PMID: 7060323.