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

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

Volume: 2 Issue: 1

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

Affiliation:

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

Abstract: 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.

Cite this article as:

Berry M. Loren and Zhao Zhiyang, An Examination of IC50 and IC50-Shift Experiments in Assessing Time-Dependent Inhibition of CYP3A4, CYP2D6 and CYP2C9 in Human Liver Microsomes, Drug Metabolism Letters 2008; 2 (1) . https://dx.doi.org/10.2174/187231208783478407