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Indirect assessment of dihydropyrimidine dehydrogenase activity in cats

Authors

  • C. F. Saba,

    Corresponding author
    1. Department of Small Animal Medicine & Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA, USA
    • Correspondence address:

      C. F. Saba

      Department of Small

      Animal Medicine and

      Surgery

      College of Veterinary

      Medicine

      University of Georgia

      501 DW Brooks Drive

      Athens, GA 30602, USA

      e-mail: csaba@uga.edu

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  • C. W. Schmiedt,

    1. Department of Small Animal Medicine & Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA, USA
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  • K. G. Freeman,

    1. Department of Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA
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  • G. L. Edwards

    1. Department of Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA
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Abstract

Use of 5-fluoropyridimine antimetabolite drugs, specifically 5-fluorouracil (5-FU), has been discouraged in cats because of adverse events including neurotoxicity and death. Causes of toxicity have never been elucidated. In humans, toxicity has been associated with ineffective metabolism secondary to deficiencies in dihydropyrimidine dehydrogenase (DPD). Direct assessment of DPD activity is challenging; determination of uracil:dihydrouracil (U:UH2) in plasma using high performance liquid chromatography (HPLC) has been reported as an indirect measurement. U:UH2 was measured in the plasma of 73 cats. Mean U:UH2 for all cats was 1.66 ± 0.11 (median 1.53, range 0.24–7.00). Seventeen (23%) cats had U:UH2 >2, a value associated with decreased DPD activity in humans. Spayed female cats had significantly lower U:UH2 as compared with intact females, and age and U:UH2 were weakly but significantly negatively correlated (r = −0.26). Studies correlating U:UH2 and 5-FU tolerability are required to further determine the validity and use of this test in cats.

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