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Hepatocyte Metabolic Stability

The liver is the major site of drug metabolism in the body, with well over 50% of marketed drugs eliminated via hepatic mediated metabolism. Hence, measurement of the rate of clearance and the identity of the metabolites of a drug is immensely important.

In addition, in support of projects, the rate of clearance values can be used to rank compounds and to predict in vivo hepatic clearance values. Hepatocytes from a variety of species can be used to understand inter-species differences and are essential when generating Dose to Human predictions. Unlike microsomal stability assays, both Phase I and Phase II metabolism can be tracked, and the rate of clearance and their metabolites formed are more likely to reflect the in vivo situation.

Sygnature’s Hepatocyte Stability assay monitors the disappearance of a substrate in the presence and absence of hepatocytes. All assays are validated by the inclusion of up to 3 species-specific positive control compounds. Data output consists of mean intrinsic clearance (Clint) and half-life (t1/2) measurements.

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