4 Enzyme Kinetics
TIMOTHYS. TRACY
4.1 INTRODUCTION
Determination of enzyme kinetic parameters for the metabolism of a new
chemical entity has become an important part of the drug discovery and
development process. Estimation of kinetic parameters such asKmandVmaxis
critical in determining the degree of involvement of a particular enzyme in the
metabolism of a compound under development since these parameters allow
for determination of the intrinsic clearance of an enzyme in the drug’s
metabolism and thus, comparison among enzymes involved. Furthermore,
these parameters determinedin vitromay be used to predict the human dose to
be given as well as the predictedin vivopharmacokinetics. Thus, it is crucial
that enzyme kinetic parameters, such as Kmand Vmax, be determined as
accurately as possible. This chapter will discuss the various types of kinetic
profiles (both typical and atypical) that are commonly observed with drug
metabolizing enzymes and the equations that allow estimation of the kinetic
parameters. In addition, enzyme inhibition kinetics will be discussed as it is
important in assessment of the drug interaction potential of a new chemical
entity. It should be noted that the outstanding works of Segel (1975) and
Cornish-Bowden (2004) are highly recommended for anyone conducting
enzyme kinetics experiments and served as the primary reference sources in the
preparation of this chapter.
Drug Metabolism in Drug Design and Development, Edited by Donglu Zhang, Mingshe Zhu
and W. Griffith Humphreys
Copyright#2008 John Wiley & Sons, Inc.
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