Sildenafil-Model

Whole-body PBPK model of sildenafil.

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 sildenafil model is intended to be used as victim drug in CYP3A4-mediated drug-drug interactions (DDI).

This whole-body PBPK model of sildenafil has been developed using in particular published pharmacokinetic clinical data by Muirhead et al. 2002 [1], Nichols et al. 2002 [2], the FDA [3], and Walker et al. 1999 [4]. The model has then been evaluated simulating a large number of clinical studies and comparing with respective observed data.

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] Muirhead GJ, Rance DJ, Walker DK, Wastall P. Comparative human pharmacokinetics and metabolism of single-dose oral and intravenous sildenafil. Br J Clin Pharmacol. (2002)

[2] Nichols DJ, Muirhead GJ, Harness JA. Pharmacokinetics of sildenafil after single oral doses in healthy male subjects: absolute bioavailability, food effects and dose proportionality. Br J Clin Pharmacol. (2002)

[3] Food and Drug Administration, Clinical Pharmacology and biopharmaceutics review of Revatio. (2009)

[4] Walker DK, Ackland MJ, James GC, Muirhead GJ, Rance DJ, Wastall P, et al. Pharmacokinetics and metabolism of sildenafil in mouse, rat, rabbit, dog and man. Xenobiotica. (1999)