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CYP Induction (mRNA) / HepaRG

Cytochrome P450 (CYP) induction by a drug can accelerate the metabolism of a co-administered victim drug significantly, causing serious drug-drug interactions.

To date induction of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, and CYP3A4 have been described. Whilst CYP1A2 induction involves the Aryl hydrocarbon receptor (AhR) and induction of CYP2B6 is mediated by the constitutive androstane receptor (CAR), the CYP2C isoforms and CYP3A4 are co-induced via the pregnane X receptor (PXR). Therefore, the current FDA guidelines suggest to investigate induction of CYP1A2, CYP2B6 and CYP3A4.

Traditionally, CYP induction has been measured via the assessment of enzyme activity in human hepatocytes. To address inter-individual variability, hepatocyte preparations from at least three donors had to be used.

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