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

Craig      Giragossian; Jennifer      LaPerle; Rachel   E.   Kosa; Sarah      Gillian

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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Drug Metabolism Letters

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

Volume: 3 Issue: 1

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

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

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.

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Giragossian Craig, LaPerle Jennifer, Kosa E. Rachel and Gillian Sarah, Impact of Time-Dependent Inactivation on the Estimation of Enzyme Kinetic Parameters for Midazolam, Drug Metabolism Letters 2009; 3(1) . https://dx.doi.org/10.2174/187231209787176353