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treat cats with occult HCM. Rapamycin, also known as sirolimus, a macrolide and inhibitor of the mechanistic (previously called mammalian) target of rapamycin (mTOR), shows promise as a novel therapeutic for feline HCM. 5 – 10 mTOR is an atypical

Open access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To compare the in vitro imMunosuppressive effects of cyclosporine and 4 novel immunosuppressive drugs on lymphocytes in whole blood collected from healthy cats.

Sample Population—Whole blood samples collected from 10 healthy adult domestic shorthair cats.

Procedure—Mitogen-stimulated lymphocyte proliferation in whole blood incubated with and without various concentrations of cyclosporine, tacrolimus, sirolimus, mycophenolic acid (MPA), or A771726 was measured by use of [3H]thymidine incorporation. Drug concentrations that resulted in a 50% inhibition of mitogen-induced proliferation (IC50) were calculated. Lymphocyte viability was determined by use of the trypan blue dye exclusion method.

Results—An obvious dose-response relationship for the antiproliferative effects of each drug was detected. Mean IC50 determined with concanavalin A was 46 nMfor cyclosporine, 9 nMfor tacrolimus, 12 nM for sirolimus, 16 nM for MPA, and 30 mM for A771726, whereas with pokeweed mitogen, mean IC50 was 33 nM for cyclosporine, 5 nMfor tacrolimus, 15 nM for sirolimus, 14 nM for mycophenolic acid, and 25 mM for A771726. Mitogen-stimulated and nonstimulated lymphocytes remained viable, regardless of drug evaluated.

Conclusions and Clinical Relevance—Tacrolimus, sirolimus, MPA, and A771726 inhibited in vitro mitogen- stimulated proliferation of feline lymphocytes in a dose-dependent manner. These novel immunosuppressive drugs may be useful for management of immune-mediated inflamMatory diseases and prevention and treatment of rejection in cats that undergo organ transplantation. (Am J Vet Res 2000;61: 906–909)

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in American Journal of Veterinary Research

Rapamycin, also known as sirolimus, was first isolated from Streptomyces hygroscopicus on Easter Island in the mid-1970s 1 and was initially characterized as an antifungal and antimicrobial agent. Since then, its immunosuppressant and

Full access
in American Journal of Veterinary Research

been used if increasing the dosage of prednisone did not result in improvement of clinical signs. Other drugs used for immunosuppression in cats include cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, and leflunomide 30 or cytotoxic drugs

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in Journal of the American Veterinary Medical Association

Shinohara ET Moretti L , et al. The role of mTOR inhibition in augmenting radiation induced autophagy . Technol Cancer Res Treat 2007 ; 6 : 433 – 448 . 53. Sarkaria JN Schwingler P Schild SE , et al. Phase I trial of sirolimus combined

Full access
in American Journal of Veterinary Research

distributions of cyclosporin and sirolimus after concomitant peroral administration to the rat: evidence for pharmacokinetic interactions . Ther Drug Monit 1998 ; 20 : 123 – 133 . 10.1097/00007691-199804000-00001 6 Aungst BJ . P-glycoprotein secretory

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in American Journal of Veterinary Research