Drug-drug-gene interactions

Many patients take several drugs at the same time and carry genetic variants in enzymes such as CYP2D6 or CYP3A. Drug-drug-gene interactions (DDGIs) arise when these factors act together, and they can hardly be studied fully in clinical trials. We predict them with models and derive dosing recommendations.

How we work

We build PBPK networks of substrates, inhibitors and inducers that take genotype and activity score into account. We make the models publicly available so that other groups and industry can use them.

Models online

Our models are available from Open Systems Pharmacology on GitHub and at models.clinicalpharmacy.me.

Selected publications

• Rüdesheim S, Loer HLH, Feick D, … Schwab M, Lehr T. A comprehensive CYP2D6 drug-drug-gene interaction network for application in precision dosing and drug development. Clin Pharmacol Ther. 2025. doi:10.1002/cpt.3604
• Kovar C, Loer HLH, Rüdesheim S, … Schwab M, Lehr T. A physiologically-based pharmacokinetic precision dosing approach to manage dasatinib drug-drug interactions. CPT Pharmacometrics Syst Pharmacol. 2024. doi:10.1002/psp4.13146
• Wojtyniak JG, Selzer D, Schwab M, Lehr T. Physiologically based precision dosing approach for drug-drug-gene interactions: a simvastatin network analysis. Clin Pharmacol Ther. 2021;109(1):201-211. doi:10.1002/cpt.2111