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ADME / Tox >> Drug-Drug Interactions >> CYP Induction

Measure CYP induction through mRNA levels

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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:

  • mRNA measurements for CYP isozymes (CYP1A2, CYP2B6 and CYP3A4) induction provide a more sensitive and reliable method than traditional enzyme activity assays
  • Assays established in accordance with the FDA Guidance on Drug Interaction Studies (2012)1
    • Cryopreserved human hepatocytes from at least three donors
    • Real time qPCR
    • Results can be used for regulatory filings
  • Combine with other drug-drug interaction studies to gain a complete profile of your new molecular entity


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drug interaction studies - study design, data analysis, and implications for dosing and labeling recommendations, draft guidance, February 2012.