Physiologically Based Pharmacokinetic (PBPK) Modeling of Metoprolol and its CYP2D6 Drug-Gene Interactions (DGIs)

Within this repository, we distribute a whole-body PBPK model of metoprolol, its enantiomers and its metabolite α-hydroxymetoprolol. The model has been carefully developed and evaluated for the prediction of (R)-metoprolol, (S)-metoprolol, racemic metoprolol and metabolite α-hydroxymetoprolol plasma concentrations after intravenous and oral administration over a wide dose range (5 to 200 mg).

The PBPK model was developed to describe the effect of genetic variants in the CYP2D6 gene on the pharmacokinetics of metoprolol. For this purpose, CYP2D6 k_cat values were optimized for different CYP2D6 activity scores.

For further details on model development and evaluation as well as extensive documentation of the modeling process, please refer to [1].

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.

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.

The model code is distributed under the GPLv2 License.

[1] Rüdesheim, S.; Wojtyniak, J.-G.; Selzer, D.; Hanke, N.; Mahfoud, F.; Schwab, M.; Lehr, T. Physiologically Based Pharmacokinetic Modeling of Metoprolol Enantiomers and α-Hydroxymetoprolol to Describe CYP2D6 Drug-Gene Interactions. Pharmaceutics 2020, 12, 1200.