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

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 K(I) and TDI potency ratio k(inact)/K(I) to within 2-fold in most cases.