Felodipine-Model

Whole-body PBPK model of felodipine.

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

This whole-body PBPK model of felodipine has been developed using in particular published pharmacokinetic clinical data by Edgar et al. 1987 [1], Bailey et al. 1996 [2], Gelal et al. 2005 [3], Bailey et al. 2003 [4], Goosen 2004 [5], Jalava et al. 1997 [6], Blychert et al. 1990 [7], Lundahl et al. 1998 [8], Bailey et al. 1995 [9], Aberg et al. 1997 [10], Bailey et al. 1993 [11], Edgar et al. 1992 [12], and Lundahl et al. 1997 [13]. 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] Edgar B, Lundborg P, Regårdh CG. Clinical pharmacokinetics of felodipine. A summary. Drugs. (1987)

[2] Bailey DG, Bend JR, Arnold JM, Tran LT, Spence JD. Erythromycin-felodipine interaction: magnitude, mechanism, and comparison with grapefruit juice. Clin Pharmacol Ther. (1996)

[3] Gelal A, Balkan D, Ozzeybek D, Kaplan YC, Gurler S, Guven H, et al. Effect of menthol on the pharmacokinetics and pharmacodynamics of felodipine in healthy subjects. Eur J Clin Pharmacol. (2005)

[4] Bailey D. Bergamottin, lime juice, and red wine as inhibitors of cytochrome P450 3a4 activity: comparison with grapefruit juice. Clinical Pharmacology & Therapeutics. (2003)

[5] Goosen TC, Cillie D, Bailey DG, Yu C, He K, Hollenberg PF, et al. Bergamottin contribution to the grapefruit juice-felodipine interaction and disposition in humans. Clin Pharmacol Ther. (2004)

[6] Jalava KM, Olkkola KT, Neuvonen PJ. Itraconazole greatly increases plasma concentrations and effects of felodipine. Clin Pharmacol Ther. (1997)

[7] Blychert E, Wingstrand K, Edgar B, Lidman K. Plasma concentration profiles and antihypertensive effect of conventional and extended-release felodipine tablets. Br J Clin Pharmacol. (1990)

[8] Lundahl JU, Regårdh CG, Edgar B, Johnsson G. The interaction effect of grapefruit juice is maximal after the first glass. Eur J Clin Pharmacol. (1998)

[9] Bailey DG, Arnold JM, Bend JR, Tran LT, Spence JD. Grapefruit juice-felodipine interaction: reproducibility and characterization with the extended release drug formulation. Br J Clin Pharmacol. (1995)

[10] Aberg J, Abrahamsson B, Grind M, Nyberg G, Olofsson B. Bioequivalence, pharmacokinetic and pharmacodynamic response to combined extended release formulations of felodipine and metoprolol in healthy volunteers. Eur J Clin Pharmacol. (1997)

[11] Bailey DG, Arnold JM, Munoz C, Spence JD. Grapefruit juice--felodipine interaction: mechanism, predictability, and effect of naringin. Clin Pharmacol Ther. (1993)

[12] Edgar B, Bailey D, Bergstrand R, Johnsson G, Regårdh CG. Acute effects of drinking grapefruit juice on the pharmacokinetics and dynamics of felodipine--and its potential clinical relevance. Eur J Clin Pharmacol. (1992)

[13] Lundahl J, Regårdh CG, Edgar B, Johnsson G. Effects of grapefruit juice ingestion--pharmacokinetics and haemodynamics of intravenously and orally administered felodipine in healthy men. Eur J Clin Pharmacol. (1997)