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Indirect assessment of dihydropyrimidine dehydrogenase activity in cats
Author(s) -
Saba C. F.,
Schmiedt C. W.,
Freeman K. G.,
Edwards G. L.
Publication year - 2013
Publication title -
veterinary and comparative oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 34
eISSN - 1476-5829
pISSN - 1476-5810
DOI - 10.1111/vco.12064
Subject(s) - cats , toxicity , neurotoxicity , uracil , tolerability , medicine , pharmacology , chemistry , adverse effect , toxicology , biochemistry , biology , dna
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: UH 2 ) in plasma using high performance liquid chromatography ( HPLC ) has been reported as an indirect measurement. U: UH 2 was measured in the plasma of 73 cats. Mean U: UH 2 for all cats was 1.66 ± 0.11 (median 1.53, range 0.24–7.00). Seventeen (23%) cats had U: UH 2 >2, a value associated with decreased DPD activity in humans. Spayed female cats had significantly lower U: UH 2 as compared with intact females, and age and U: UH 2 were weakly but significantly negatively correlated ( r = −0.26). Studies correlating U: UH 2 and 5‐ FU tolerability are required to further determine the validity and use of this test in cats.