Improving In Vivo Predictions from In Vitro Hepatocyte Models

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January 16, 2024

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  • Speaker: Kenneth R. Brouwer, PhD, RPh, Vice President of Technology, ADME-Tox, BioIVT Abstract: In both in vitro systems and in vivo, it is the unbound intracellular concentration (ICC) that is the driving force for processes that occur inside the hepatocyte. Achievement of an in vivo relevant ICC requires a polarized whole-cell system that integrates uptake into the hepatocyte, metabolism, and efflux (basolateral and canalicular) from the hepatocyte. Extensive protein binding can limit the uptake of many drugs, however for some drugs the estimation of intracellular concentration, and hepatic clearance cannot be correctly predicted based on the free (unbound) drug concentration. Additionally, studies have shown that transporters can be upregulated similar to metabolic proteins, resulting in increased uptake and/or efflux. Use of polarized whole-cell models and optimized culture conditions for in vitro systems may improve predictions of a drug’s in vivo properties and effects.

    Analytical TechniquesBiopharmaCell CultureDrug Discovery

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