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We conduct metabolic stability assays to help our clients predict the human in vivo rate of disappearance of a test compound over time. Data from our in vitro models is used to calculate intrinsic clearance and inform other metabolism, DDI, and hepatic clearance studies.
We recommend the following models based on the rate of compound clearance and length of study required:
Compounds with high uptake and clearance can be investigated using liver microsomes or suspended hepatocytes. Microsomal assays primarily assess metabolism by the cytochrome P450 system (phase 1); hepatocyte assays more broadly assess the overall cellular metabolism of the test compound (phase I and II). Incubations can be carried out in mouse, rat, dog, or monkey microsomes or hepatocytes to compare with human data.
We use HEPATOPAC Technology to create stable hepatocyte cultures that can remain viable for up to 28 days. We recommend HEPATOPAC cultures for compounds that have low uptake and clearance and any experimental design requiring long-term viable hepatocyte cultures. The limited lifespan of microsome and suspended hepatocyte cultures limits their utility in determining clearance for stable compounds.
Because of their longevity and stable enzymatic functions, HEPATOPAC cultures allow for the complete metabolism of pharmaceutical compounds. Compared to conventional systems, the HEPATOPAC model has demonstrated improved IVIVC in detecting primary and secondary excretory metabolites and can be used to stratify low turnover compounds in a chemical series. HEPATOPAC cultures are available for the following species: human, rat, dog, monkey, and multi-species plates.