Measure CYP induction through mRNA levels
In additional to playing play a major role in the metabolic fate of drugs, cytochrome P450 (CYP) enzymes are major targets in drug-drug interactions (DDIs). Drug induced inhibition of CYP enzymatic activity is one important cause for DDI, but it not alone sufficient to assess the potential to induce DDI. CYP enzymes can be transcriptionally induced by many xenobiotics including some drugs, through the mediation of nuclear receptors. Therefore, understanding the potential of new molecular entities (NMEs) to induce CYP expression is important to minimize DDI liability.
CYP induction is traditionally determined by measuring enzymatic activity in cultured primary hepatocytes; however, due to enzyme inhibition, cytotoxicity, or other effects, this assay is prone to false negatives. In order to address the growing need for robust, sensitive assays to measure CYP induction, Eurofins has developed CYP assays which measure the mRNA level of the targeted CYP genes. As the preferred method to measure CYP induction, mRNA analysis is less prone to false negatives than traditional activity-based assays and follows FDA and EMA Guidance (2012).
Advantages of CYP induction profiling with Eurofins:
Figure 1. CYP3A4 gene induction profile in three hepatocyte sources
1FDA Guidance for Industry: drug interaction studies - study design, data analysis, and implications for dosing and labeling recommendations, draft guidance, February 2012.