Pharmacogenetics of Drug Metabolism

Zeruesenay Desta, David A. Flockhart

Research output: Chapter in Book/Report/Conference proceedingChapter

3 Scopus citations

Abstract

In this chapter, common genetic polymorphisms affecting pharmacokinetics via effects on drug metabolism are outlined, and their clinical relevance is discussed. The goal of effective and safe therapy of many drugs is made difficult by large interpatient variability in response and toxicity, and this problem is a substantial burden for patients, their caretakers, and the health-care system. For many drugs, the response to chronic administration is determined by the area under the plasma concentration time curve, during a dosing interval at steady state, a measure of drug exposure. An increasing number of drug-metabolizing enzymes have been shown to result in large pharmacokinetic changes through a variety of different mechanisms. Drugs that are most affected are those that have a dominant route of clearance by a genetically polymorphic enzyme. The effects of such pharmacokinetic changes are most important in settings where clinically important pharmacodynamic change ensues. Pharmacogenetic tests that are most valuable are those for specific drugs for which the prediction of activity or adverse effects is important and difficult to anticipate given our current clinical tools and technologic capability. Although data from a variety of platforms documenting a wide range of genetic variability are being accumulated rapidly and clinical genetic tests have been recommended or implemented for drugs such as mercaptopurine, azathioprine, clopidogrel, warfarin, and irinotecan, there is still a great need for well-designed, prospective clinical trials that test pharmacogenetic approaches versus standard practice.

Original languageEnglish (US)
Title of host publicationClinical and Translational Science
Subtitle of host publicationPrinciples of Human Research: Second Edition
PublisherElsevier Inc.
Pages327-345
Number of pages19
ISBN (Print)9780128021019
DOIs
StatePublished - Jan 1 2017

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Keywords

  • Drug metabolism
  • Drug-metabolizing enzymes
  • Drug-metabolizing genes
  • Genetic polymorphisms
  • Pharmacodynamics
  • Pharmacogenetics
  • Polymorphic enzyme

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Desta, Z., & Flockhart, D. A. (2017). Pharmacogenetics of Drug Metabolism. In Clinical and Translational Science: Principles of Human Research: Second Edition (pp. 327-345). Elsevier Inc.. https://doi.org/10.1016/B978-0-12-802101-9.00018-1