Assessment of plasma uracil-to-dihydrouracil concentration ratio as an indicator of dihydropyrimidine dehydrogenase activity in clinically normal dogs and dogs with neoplasia or renal insufficiency

Schmiedt, Chad W.; Saba, Corey; Freeman, Kimberly G.; Edwards, Gaylen L.

doi:10.2460/ajvr.73.1.119

Cited by 2 publications

(8 citation statements)

References 23 publications

(48 reference statements)

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“…Ratios were variable amongst cats, and mean and median U:UH 2 in all cats were 1.66 and 1.53, respectively. These are comparable to mean and median ratios reported in humans (1.49 and 1.5, respectively), as well as in dogs (1.55 and 1.38, respectively) . Approximately 23% had a U:UH 2 >2, a value associated with abnormal DPD activity in humans.…”

Section: Discussionsupporting

confidence: 84%

“…Interestingly, neuter status was also the only significant factor we identified in dogs, and spayed or neutered dogs had lower U:UH 2 than intact dogs. In the canine study, this finding was more pronounced in males . It remains unknown, however, if being intact increases U:UH 2 within the normal range or if intact cats and dogs are more likely to have U:UH 2 outside of the range of normal.…”

Section: Discussionmentioning

confidence: 76%

“…The high performance liquid chromatography (HPLC) method was a modification of a previously described technique –. Plasma samples were thawed on ice and a 500 µL aliquot of the sample was combined with 20 µL of 5% phosphoric acid and vortexed for 5 s. Six millilitres of a mixture of n‐propanol:ether (16:84, v/v) were added to the tube containing the sample and vortexed for 5 min.…”

Section: Methodsmentioning

confidence: 99%

“…We have demonstrated that this assay is simple to perform and have reported U:UH 2 in 101 dogs. Of the dogs surveyed, 14% had U:UH 2 >2, and intact dogs had a significantly higher U:UH 2 compared with neutered or spayed dogs …”

Section: Introductionmentioning

confidence: 99%

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Indirect assessment of dihydropyrimidine dehydrogenase activity in cats

Saba

Schmiedt

Freeman

et al. 2013

Vet Comparative Oncology

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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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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 76%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Indirect assessment of dihydropyrimidine dehydrogenase activity in cats

Saba

Schmiedt

Freeman

et al. 2013

Vet Comparative Oncology

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“…Ingestion of 5‐FU has resulted in fatal neurotoxicities in both cats and dogs . This could potentially be associated with decreased concentrations of DPD in veterinary patients; approximately 25% of cats and 14% of dogs had uracil:dihydrouracil concentrations greater than a value associated with decreased DPD in humans …”

Section: Introductionmentioning

confidence: 99%

Concurrent 5‐fluorouracil and carboplatin for the treatment of canine carcinomas

Menard

Flesner

Glahn

et al. 2018

Vet Comparative Oncology

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5-Fluorouracil (5-FU) is used in combination chemotherapy protocols for human head and neck cancer and other epithelial neoplasms. However, a paucity of literature describing use of this drug in veterinary oncology exists, likely due to previous reports of fatal neurotoxicity in both dogs and cats, mainly due to ingestion of human creams. The primary aim of this retrospective study was to report the safety of concurrent 5-FU and carboplatin in canine carcinomas. Secondarily, we aimed to look at the efficacy of the combination using overall response rate in treated dogs. Medical records were searched from 2007 to 2017 for dogs treated with both agents; 24 dogs met inclusion criteria. Carboplatin dosages ranged from 180 to 250 mg/m (median 200 mg/m ); 5-FU dosage was 150 mg/m . Fourteen dogs had myelosuppression, ranging from Grade I to asymptomatic Grade IV; thrombocytopenia was more common than neutropenia. Gastrointestinal upset was uncommon, with only seven dogs having Grade I or II nausea, vomiting or diarrhoea. No cases were hospitalized for any of the above toxicities. One dog had an episode of ataxia, which could not be differentiated between otitis and 5-FU neurotoxicity. This protocol is well tolerated. Response rate in the gross disease setting was 43% (three complete responses, three partial responses). Prospective analysis of this combination protocol, and potentially 5-FU with other platinum agents, is warranted in the treatment of canine carcinomas.

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Assessment of plasma uracil-to-dihydrouracil concentration ratio as an indicator of dihydropyrimidine dehydrogenase activity in clinically normal dogs and dogs with neoplasia or renal insufficiency

Cited by 2 publications

References 23 publications

Indirect assessment of dihydropyrimidine dehydrogenase activity in cats

Indirect assessment of dihydropyrimidine dehydrogenase activity in cats

Concurrent 5‐fluorouracil and carboplatin for the treatment of canine carcinomas

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