title: Indirect assessment of dihydropyrimidine dehydrogenase activity in cats.
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.
authors.affiliation: Department of Small Animal Medicine & Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
authors.forename: C F
authors.initials: CF
authors.lastname: Saba
authors.forename: C W
authors.initials: CW
authors.lastname: Schmiedt
authors.forename: K G
authors.initials: KG
authors.lastname: Freeman
authors.forename: G L
authors.initials: GL
authors.lastname: Edwards
mesh_terms: D000375:Aging; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000378:metabolism; D002371:Cat Diseases / Q000139:chemically induced*; D002415:Cats; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008297:Male; D014498:Uracil / Q000031:analogs & derivatives* / Q000097:blood* / Q000378:metabolism
chemical_list: D000964:Antimetabolites, Antineoplastic; C007419:dihydrouracil; D014498:Uracil; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil
keywords: chemotherapy; comparative oncology; epidemiology; oncology; small animal