Case Study 4: Application of Basic Enzyme Kinetics to Metabolism Studies-Real-Life Examples

Methods Mol Biol. 2021:2342:665-684. doi: 10.1007/978-1-0716-1554-6_23.

Abstract

An appreciation of enzyme kinetic principles can be applied in a number of drug metabolism applications. The concept for this chapter arose from a simple discussion on selecting appropriate time points to most efficiently assess metabolite profiles in a human Phase 1a clinical study (Subheading 4). By considering enzyme kinetics, a logical approach to the issue was derived. The dialog was an important learning opportunity for the participants in the discussion, and we have endeavored to capture this experience with other questions related to determination of Km and Vmax parameters, a consideration of the value of hepatocytes vs. liver microsomes, and enzyme inhibition parameters.

Keywords: Cytochrome P450; DDI; Enzyme kinetics; Hepatocytes; Inhibition; Liver microsomes; Metabolite identification.

MeSH terms

  • Algorithms
  • Clinical Trials, Phase I as Topic
  • Cytochrome P-450 Enzyme System / metabolism*
  • Drug Dosage Calculations
  • Humans
  • Kinetics
  • Metabolomics / methods*
  • Microsomes, Liver / enzymology
  • Microsomes, Liver / metabolism
  • Pharmaceutical Preparations / administration & dosage*
  • Pharmaceutical Preparations / metabolism

Substances

  • Pharmaceutical Preparations
  • Cytochrome P-450 Enzyme System