Drug metabolism and clearance
HepaRG™ cells are classified as an “average human hepatocyte population” and express multiple functional Phase 1 and 2 drug metabolising enzyme (DME) activities comparable to levels in cultures of primary human hepatocytes. This makes them a much better model for metabolism and clearance studies than any other cell line currently available. The prediction of in-vivo intrinsic clearance of a panel of drugs has been shown to be mostly within 2‑fold using HepaRG™ cells. Moreover, the sustained presence of DMEs over weeks makes them ideal for measuring the clearance of low clearance compounds.
Metabolite ID
HepaRG™ cells have a full complement of DMEs, cofactors and transporter proteins and the profile of DME activities and expression provides a good representation of that in primary human hepatocytes. Together with the high stability of the enzymes, this makes these cells ideal for producing relevant drug metabolites in sufficient quantities to enable metabolite identification.
DME induction assays
HepaRG™ cells express functional transcription factors involved in the regulation of DMEs. These cells are responsive to prototypical inducers of CYP1A1/2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, and CYP3A4 and can be used to predict in-vivo CYP3A4 induction of test compounds by constructing a calibration curve using known potent and mild inducers of this CYP (“AUC/F2” or “RIS”). The protocol for CYP induction using HepaRG™ cells has been accepted by ESAC and an OECD guideline for use of HepaRG™ cells in induction studies is in preparation.
DME inhibition assays
The high levels of DMEs in HepaRG™ cells makes them ideal for inhibition screening studies. The IC50 values of a panel of CYP inhibitors using HepaRG™ cells correlated very well with those determined in primary human hepatocytes. Time-dependent inhibition can also be investigated using these cells.
Functional transporter assays
HepaRG™ cells express a number of uptake and efflux drug transporters and form tight junctions and bile canaliculi, making them ideal for uptake and biliary secretion studies.
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