As part of the clinical pharmacological service, the IKP provides PGx diagnostics to in- and out-patients using various technologies which have been established and validated in the molecular and chemical analytics core facilities. PGx diagnostics is not restricted to genetic analyses, but also includes - if necessary - biochemical tests as well as the quantitation of PGx drugs and their respective metabolites in different specimens (e.g. serum, urine, blood spots).

Currently, various methods are available at IKP to detect frequent genetic variants in >20 pharmacogenes. Molecular genetic testing procedure was built according the German Gene Diagnostic Law (Gendiagnostikgesetz) and is currently prepared to fulfill the European in vitro diagnostics regulation. As member of the assessor team (R Tremmel, IKP) of a PGx testing and interpretation scheme (www.emqn.org), the quality of the PGx tests is yearly ensured. 

For quantitation of drug levels and respective metabolites a mass spectrometry-based assay has been established at the Chemical Analytics & Synthesis core facility at the IKP for simultaneous quantitation of >30 agents, known to be affected by pharmacogenes. 

In addition to routine genetic PGx diagnostics, quantitation of drug levels in blood can be helpful in patients with extreme phenotypes such as severe ADR under drug therapy. Of note, since decades therapeutic drug monitoring is well-established and part of clinical routine for drugs with a narrow therapeutic window. Other reasons, which are justifying the determination of drug and metabolite levels are as following:

  • Monitoring of drug levels in blood or other tissues (e.g. in erythrocytes) if PGx-related dose reduction has been performed and subsequent monitoring of drug levels is required. The best example is TPMT deficiency for instance in ALL children, who receive about 10% of standard thiopurine dosage acc. to the BFM ALL protocol. Since therapeutic outcome is determined by blood leukocytes, individual dosing based on red blood cell concentrations of the active thiopurine metabolites (TGN) is mandatory. 
  • The rapid metabolizer phenotype for CYP2D6 can only in part be detected by the CYP2D6 gene amplification. Therefore, quantitation of plasma levels and CYP2D6 dependent metabolites is clinically important particularly in patients with drug failure.
  • Supposed drug-drug-gene interactions