Use of Capecitabine to Prevent Acute Renal Allograft Rejection in Dog Erythrocyte Antigen‐Mismatched Mongrel Dogs

Abstract

A CAP-CsA-prednisolone protocol is an effective, oral immunosuppressive regimen for prevention of allograft rejection in DEA-mismatched mongrel dogs. For clinical application, identification of patients susceptible to toxic side effects would be necessary.

Histopathologic Evidence of Capecitabine Corneal Toxicity in Dogs

“…1, 7 CPC has also been used as an immunosuppressive agent to counteract canine renal transplant rejection. 4 Ocular adverse effects were noted in this renal study and led to an examination by a veterinary ophthalmologist and veterinary ophthalmic pathologist. The results of those ophthalmic examinations are reported here.…”

“…7 Adverse effects have included hyperexcitability, altered mentation, seizures, gastric ulceration, and lymphoplasmacytic enteritis. 4, 6 Like 5-FU, eye irritation with corneal deposits has been reported with the use of CPC in humans. However, the histopathology of CPC corneal toxicity has not been described (Roche, Pharmaceuticals: Xeloda.…”

“…The methods have been reported elsewhere. 4, 6 In brief, 6 adult, female, unrelated, purpose-bred research mongrels were used in a study that evaluated the effectiveness of CPC in preventing renal transplant rejection. Renal transplants were performed with the dogs under general anesthesia.…”

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

“…3 Veterinary use of capecitabine has primarily been investigated as an immunosuppressant following renal transplantation in dogs. [4][5][6] In those studies, [4][5][6] capecitabine was effective in preventing rejection of renal allografts in dog erythrocyte antigenmismatched mongrel dogs, but fatal, irreversible neurotoxicosis, which was potentially attributed to the drug, developed in 2 of 8 allograft recipients. This unacceptable severity of toxic effects has prohibited further clinical investigation.…”

“…This unacceptable severity of toxic effects has prohibited further clinical investigation. [4][5][6] Because the maximally tolerated dosages of these drugs are unknown, it is plausible that some of the reported toxic effects may be alleviated with optimized, species-specific dosing regimens. However, the toxic effects may also be related to insufficient activity of DPD, the rate-limiting enzyme in metabolism of 5-FU.…”