High Throughput Quantitative Assessment of CYP Inactivation Using 2 Concentration Points

Title: High Throughput Quantitative Assessment of CYP Inactivation Using 2 Concentration Points

Volume: 3 Issue: 2

Author(s): Daniel Albaugh, Thomas Farrell, Michael Langan and W. George Lai

Affiliation:

Keywords: Cytochrome P450, enzyme inactivation, KI, kinact

Abstract: 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.

Cite this article as:

Albaugh Daniel, Farrell Thomas, Langan Michael and Lai George W., High Throughput Quantitative Assessment of CYP Inactivation Using 2 Concentration Points, Drug Metabolism Letters 2009; 3 (2) . https://dx.doi.org/10.2174/187231209788654063