Drug Metabolism Letters

Zhiyang Zhao
Amgen
Cambridge, MA
USA

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High Throughput Quantitative Assessment of CYP Inactivation Using 2 Concentration Points

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

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.

Keywords: Cytochrome P450, enzyme inactivation, KI, kinact

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Article Details

VOLUME: 3
ISSUE: 2
Year: 2009
Page: [78 - 82]
Pages: 5
DOI: 10.2174/187231209788654063
Price: $58