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