Pharmacogenetics of Drug Metabolism

David A. Flockhart, Zeruesenay Desta

Research output: Chapter in Book/Report/Conference proceedingChapter

5 Scopus citations

Abstract

In this chapter, common genetic polymorphisms affecting pharmacokinetics via effects on drug metabolism are outlined and their clinical relevances are 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 healthcare system. For many drugs, the response to chronic administration is determined by the area under the plasma concentration time curve (AUC), 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. Pharmacogenetics 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, warfarin, irinotecan, and tamoxifen, there is still a great need for well-designed, prospective clinical trials that test pharmacogenetic approaches versus standard practice. © 2009

Original languageEnglish (US)
Title of host publicationClinical and Translational Science
PublisherElsevier Inc.
Pages301-317
Number of pages17
ISBN (Print)9780123736390
DOIs
StatePublished - Dec 1 2009

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ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Flockhart, D. A., & Desta, Z. (2009). Pharmacogenetics of Drug Metabolism. In Clinical and Translational Science (pp. 301-317). Elsevier Inc.. https://doi.org/10.1016/B978-0-12-373639-0.00021-2