title: Modeling kinetic data from in vitro drug metabolism enzyme experiments.
abstract: Modeling of in vitro enzyme kinetic data derived from drug metabolism experiments can greatly facilitate the drug development process because estimation of kinetic parameters can facilitate decision making regarding whether to continue development of a compound. From this information, predictions can be made regarding the "metabolic stability" of a compound and even the in vivo intrinsic clearance of the drug. Many drugs exhibit typical Michaelis-Menten-type kinetics in vitro that result in a hyperbolic kinetic profile from which Km and Vm can be readily estimated. However, it is increasingly being recognized that many drug compounds exhibit "atypical" enzyme kinetics in vitro, requiring use of more complex kinetic models for data fitting and parameter estimation. These atypical kinetic profiles may include sigmoidal kinetics (autoactivation), biphasic kinetics, substrate inhibition kinetics, and heterotropic cooperativity (activation). This article briefly summarizes the types of equations necessary to adequately model both typical and atypical kinetic profiles in order to facilitate correct estimation of the relevant kinetic parameters.
authors.affiliation: Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, USA. tracy017@umn.edu
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Tracy
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Hummel
mesh_terms: D000465:Algorithms; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000378:metabolism*
chemical_list: D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System