Cytochrome p450 (CYP) enzymes are responsible for the Phase I metabolism of most drugs. And, it is noteworthy that the expression of cytochrome p450 (CYP) genes are predominantly regulated by ligand-activated receptors/transcription factors such as pregnane X receptor (PXR, NR1I2), constitutive androstane receptor (CAR, NR1I3), aryl hydrocarbon receptor (AhR), farnesoid x receptor (FXR, NR1H4), glucocorticoid receptor (GR, NR3C1), and to lesser degrees liver X receptors (LXR, NR1C3), vitamin D receptor (VDR, NR1I1), and peroxisome proliferator-activated receptor alpha (PPARα, NR1C1). Consequently, drugs that activate any of these xenobiotic sensing receptors can dramatically change the endogenous levels of CYP expression in the liver, potentially impacting the rate of their own metabolism, as well as the metabolism of all other co-administered drugs. Of particular concern are metabolic outcomes that transform a drug to greater potency, or to an altered bioactivity.
Assessing drug-induced changes in the expression of CYP genes provides a reliable predictive indicator of altered (either heightened or inhibited) metabolic activities leading to drug-drug interactions in vivo. Cytochrome p450 enzymes with the greatest clinical relevance belong to CYP1, 2, and 3 families. It is estimated that they are involved in the metabolism of 70-80% of drugs currently on the market. For example, CYP3A4 is estimated to be involved in ~30% of all prescription drugs.
INDIGO's assay kit for the Expression Profiling of Clinically Relevant CYPs contains optimized reagents for the culturing and treatment of upcyte® hepatocytes to assess drug-induced changes in seven clinically-relevant CYPs: CYP3A4. CYP1A1, CYP2B6, CYP2C8, CYP2C9, CYP2C19, and CYP2E1.