E-clomiphene-Model

Parent-metabolite PBPK model of (E)-clomiphene and its metabolites (E)-4-hydroxyclomiphene, (E)-N-desethylclomiphene and (E)-4-hydroxy-N-desethylclomiphene including various CYP2D6 drug-gene interactions (DGI).

Repository files

Within this repository, we distribute a whole-body parent-metabolite PBPK model of (E)-clomiphene and its metabolites (E)-4-hydroxyclomiphene, (E)-N-desethylclomiphene and (E)-4-hydroxy-N-desethylclomiphene. The model was developed using plasma concentration-time and renal excretion-time profiles of various CYP2D6 activity scores from a pharmacokinetic panel study as well as from four published clinical studies. The model is able to describe and predict CYP2D6 DGIs in six different CYP2D6 activity score groups.

For further details, quantitative model evaluation and extensive documentation please refer to [1].

Version information

Published in PK-Sim Version 9.1 and migrated to PK-Sim Version 12 without changes.

Code of conduct

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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.

Reference

[1] Kovar, C.; Kovar, L.; Rüdesheim, S.; Selzer, D.; Ganchev, B.; Kröner, P.; Igel, S.; Kerb, R.; Schaeffeler, E.; Mürdter, T.E.; Schwab, M.; Lehr, T. Prediction of Drug–Drug–Gene Interaction Scenarios of (E)-Clomiphene and Its Metabolites Using Physiologically Based Pharmacokinetic Modeling. Pharmaceutics 2022, 14, 2604.