Indirect assessment of dihydropyrimidine dehydrogenase activity in cats.
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.
['Saba|C F|CF|', 'Schmiedt|C W|CW|', 'Freeman|K G|KG|', 'Edwards|G L|GL|']
D000375:Aging D000818:Animals D000964:Antimetabolites, Antineoplastic D002371:Cat Diseases D002415:Cats D042943:Dihydrouracil Dehydrogenase (NADP) D005260:Female D005472:Fluorouracil D015971:Gene Expression Regulation, Enzymologic D008297:Male D014498:Uracil
chemotherapy comparative oncology epidemiology oncology small animal