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Drug Metabolism Letters


ISSN (Print): 1872-3128
ISSN (Online): 1874-0758

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

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

Volume 3, Issue 1, 2009

Page: [45 - 53] Pages: 9

DOI: 10.2174/187231209787176353

Price: $65


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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