Impact of time-dependent inactivation on the estimation of enzyme kinetic parameters for midazolam.
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.
Pharmacokinetics, Dynamics, and Drug Metabolism, Pfizer Global Research and Development, Groton, Connecticut 06340, USA. Craig.Giragossian@Pfizer.com
Craig
C
Giragossian
Jennifer
J
LaPerle
Rachel E
RE
Kosa
Sarah
S
Gillian
D000465:Algorithms; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D004798:Enzymes / Q000378:metabolism*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D007700:Kinetics; D008874:Midazolam / Q000493:pharmacokinetics*; D015233:Models, Statistical; D021241:Spectrometry, Mass, Electrospray Ionization
D004798:Enzymes; D006993:Hypnotics and Sedatives; D008874:Midazolam