Impact of time-dependent inactivation on the estimation of enzyme kinetic parameters for midazolam

Drug Metab Lett. 2009 Jan;3(1):45-53. doi: 10.2174/187231209787176353.


Enzyme kinetic parameters for midazolam were time-dependent in human liver microsomes, under initial velocity conditions. V(max) and K(m) 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.

MeSH terms

  • Algorithms
  • Biotransformation
  • Chromatography, High Pressure Liquid
  • Computer Simulation
  • Data Interpretation, Statistical
  • Enzymes / metabolism*
  • Humans
  • Hypnotics and Sedatives / pharmacokinetics*
  • In Vitro Techniques
  • Kinetics
  • Midazolam / pharmacokinetics*
  • Models, Statistical
  • Spectrometry, Mass, Electrospray Ionization


  • Enzymes
  • Hypnotics and Sedatives
  • Midazolam