Impact of Time-Dependent Inactivation on the Estimation of Enzyme Kinetic Parameters for Midazolam

Author(s): Craig Giragossian, Jennifer LaPerle, Rachel E. Kosa, Sarah Gillian.

Journal Name: Drug Metabolism Letters

Volume 3 , Issue 1 , 2009

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Abstract:

Enzyme kinetic parameters for midazolam were time-dependent in human liver microsomes, under initial velocity conditions. Vmax and Km decreased up to 3.7 and 3.1-fold, respectively, for 10 min compared to 1 min incubations. Mathematical models describing the relationship between inactivation and the time-dependency of enzyme kinetic parameter estimates were derived and discussed.

Keywords: Enzyme kinetics, midazolam, mechanism based inactivation, time-dependent inactivation

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Article Details

VOLUME: 3
ISSUE: 1
Year: 2009
Page: [45 - 53]
Pages: 9
DOI: 10.2174/187231209787176353

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