An Examination of IC50 and IC50-Shift Experiments in Assessing Time-Dependent Inhibition of CYP3A4, CYP2D6 and CYP2C9 in Human Liver Microsomes

Author(s): Loren M. Berry, Zhiyang Zhao

Journal Name: Drug Metabolism Letters

Volume 2 , Issue 1 , 2008

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The relationship between time-dependent inactivation (TDI) and IC50 is examined using a consolidated method for evaluating CYP450 inhibition during drug discovery. An IC50 fold-shift of > 1.5 indicated significant TDI potency. Further, the “shifted IC50” could be used to estimate, the KI and TDI potency ratio kinact/KI to within 2-fold in most cases.

Keywords: Cytochrome P450, drug interactions, in vitro models, inhibition, microsomes, time-dependent inactivation

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Article Details

Year: 2008
Page: [51 - 59]
Pages: 9
DOI: 10.2174/187231208783478407

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PDF: 135