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Comparison of XenoTech Hepatocytes to HepaRG® Cell Line

  • Published on May 18, 2014
  • Drug Metabolism
  • Scientific Posters

Full Title

Determination of Low Intrinsic Clearance Values using Primary Human Hepatocytes and the HepaRG® Cell Line – A Comparison of Methods
Svanberg, et al – AstraZeneca R&D

Abstract

Oral drugs typically require effective half lives in the region of 10 – 20 h for once or twice daily dosing. For candidate drugs with low distribution volumes it is necessary to define intrinsic clearance (CLint) values of 0.1 – 1µL/min/million Human hepatocytes (Grime et al., 2013). We wanted to compare in vitro systems that potentially can provide a solution to the problem of robustly defining low CLint values in Human hepatocytes.

Recently the HepatoPac™ Platform and a novel relay suspension method (Di et al., 2012) have shown promising results producing reliable low CLint values. XenoTech have made a well characterized plateable pool of cryopreserved Human hepatocytes (5 donors) commercially available, which makes plated hepatocytes methods attractive to evaluate. Also of interest is the HepaRG®human hepatoma cell line, since it offers stable expression of drug metabolising enzymes (DMEs) (Kanebratt et al., 2008, Aninat et al., 2006). We are evaluating all four methods but this poster focuses on HepaRG & plated primary hepatocytes since data from Hepatopac and Relay at present are inconclusive.

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