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Kye Sook Lee and Sang Kyum Kim Direct and metabolism-dependent cytochrome P450 inhibition assays for evaluating drug–drug interactions Journal of Applied Toxicology 33

Version of Record online: 14 SEP 2011 | DOI: 10.1002/jat.1720

We developed methods for evaluating inhibitory potential of eight human cytochrome P450 isoforms using substrate cocktail, human liver microsomes and liquid chromatography/tandem mass spectrometry. Our methods can distinguish between a direct inhibition and a metabolism-dependent inhibition (MDI) based on shift of IC50 values following preincubation with tested compound and NADPH. These CYP inhibition assays are considered to be useful tools for evaluating both direct inhibition and MDI at an early stage of the drug discovery and development process.

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