To provide a fast and quantitative assessment of CYP inactivation in the drug discovery stage, a mathematical model was derived to calculate enzyme inactivation parameters, kinact and KI, based on experimental data obtained from 2 concentrations of enzyme inactivator. With CYP3A4 inactivators across a range of inactivation potencies, this novel method provided expected rank-ordering of CYP3A4 inactivation. Furthermore, the kinact and KI values obtained in the two-concentration format correlate generally well with the parameters obtained in the six-concentration format.
Keywords: Cytochrome P450, enzyme inactivation, KI, kinact
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