Thiopurine methyltransferase activity in red blood cells of dogs

Linda Benjamin Kidd, Oreste E. Salavaggione, Carol L. Szumlanski, Jackie L. Miller, Richard M. Weinshilboum, Lauren Trepanier

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Thiopurine methyltransferase (TPMT) is an important enzyme in the metabolism of thiopurine medications such as azathioprine. In humans, activity varies widely among individuals, primarily because of genetic polymorphisms. Low TPMT activity increases the risk of myelosuppression from azathioprine and 6-mercaptopurine, whereas high TPMT activity is associated with poor drug efficacy. The purpose of this study was to determine whether dogs also show a wide range of TPMT activity. Heparinized blood samples were obtained from 177 dogs associated with a veterinary teaching hospital. Red blood cell (RBC) TPMT activity was measured by means of a modification of a radiochemical method as established for use in people. TPMT activity varied across a 9-fold range (7.9-71.8 U of RBC per milliliter; median, 21.7). Variation in TPMT activity was not associated with age, sex, or neutering status. Giant Schnauzers had much lower TPMT activity (7.9-20 U of RBC per milliliter; median, 13.1; P < .001) than did other breeds, and Alaskan Malamutes had much higher TPMT activity (22.7-71.8 U of RBC per milliliter; median, 36.0; P < .001) than did other breeds. Such variations in TPMT activity in the canine population and within groups of related dogs could affect thiopurine drug toxicity and efficacy in canine patients.

Original languageEnglish (US)
Pages (from-to)214-218
Number of pages5
JournalJournal of Veterinary Internal Medicine
Volume18
Issue number2
DOIs
StatePublished - Mar 1 2004

Keywords

  • Drug metabolism
  • Drug toxicity
  • Pharmacogenetics

ASJC Scopus subject areas

  • veterinary(all)

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