Phenotypic model-based prediction of pharmacogenetic dose adjustments in situations of two involved drug metabolizing enzymes: Modeling drug-gene-gene interactions and drug-drug-gene interactions

• Applicant: Professorin Dr. Julia Stingl
• Subject Area: Pharmacology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 574958526

The goal of this project is to develop precise, quantitative dose recommendations for drugs metabolized by two polymorphic enzymes—particularly CYP2C19 and CYP2D6. Building on the insight that pharmacogenetic variability can also be used to quantitatively estimate changes in drug clearance due to drug interactions, the project aims to create a model that incorporates both genetic polymorphisms and phenoconversion—changes in enzyme activity caused by co-medication.The project focuses on four main objectives: Building a continuously updated, open-access database of pharmacokinetic study data on the pharmacogenetic effects of CYP2D6 and CYP2C19. Designing and applying in vitro test systems for combined genotypes in order to fill data gaps. Developing models that integrate CYP2D6 and CYP2C19 pharmacogenetic information simultaneously to predict drug clearance and guide dose adjustments. Investigating substrate-specific differences in selected pharmacogenetic alleles through targeted in vitro analyses. The results are expected to improve drug safety in clinical practice—especially in complex cases involving polypharmacy. Methodologically, the project combines Bayesian meta-analyses of clinical studies with the integration of real-world data from therapeutic drug monitoring (TDM) in Norway, supplemented by experimental validation using recombinant enzyme systems and overexpressing cell lines.

• DFG Programme: Research Grants