An Evaluation of Leflunomide in the Canine Renal Transplantation Model1

Immunosuppression with a combination of the leflunomide analog, FK778, and microemulsified cyclosporine for renal transplantation in mongrel dogs

“…Acute postoperative intestinal intussusception is reported as a frequent complication of experimental renal transplantation in dogs, occurring in up to 25% of animals (21), and has been observed with a wide range of immunosuppressive protocols, including combinations of leflunomide and cyclosporine (13,14). In both our studies, dogs were treated with an opioid (morphine or oxymorphone), which increases intestinal smooth-muscle tone and decreases propulsive activity, and is reported to reduce the prevalence of intestinal intussusception in dogs after transplantation (22).…”

“…Gastrointestinal adverse effects are common in dogs treated with immunosuppressive drugs, such as tacrolimus (27,28), mycophenolate mofetil (29), and sirolimus (rapamycin) (29,30). Moreover, gastrointestinal side effects were described in previous studies of leflunomide in canine renal transplantation (13,14). Myocardial necrosis was noted in two of seven dogs treated with the combination of FK778 and Neoral.…”

“…In mongrel dogs undergoing renal-allograft transplantation, leflunomide alone produced a moderate increase in animal survival times, and a combination of leflunomide and a subtherapeutic dose of the oil-based formulation of cyclosporine (Sandimmune, Novartis Pharmaceuticals Corporation, East Hanover, NJ) significantly extended the mean survival time (13,14). We have previously shown that a combination of FK778 (MNA715) and the microemulsified formulation of cyclosporine (Neoral, Novartis) reduced the histologic changes associated with acute allograft rejection in dogs (15).…”

Successful treatment of acyclovir-resistant herpes simplex virus type 2 proctitis with leflunomide in an HIV-infected man

“…Leflunomide [N-(4-trifluoromethylphenyl)-methylisoxazol-4-carboxamide] is FDA-approved for the treatment of rheumatoid arthritis and has been shown to be an effective immunosuppressive agent in animal transplant models [17][18][19] and in clinical trials in human transplant recipients. 20 The active metabolite of leflunomide, A77 1726, teriflunomide [N-(4-trifluoromethylphenyl)-2-cyano-3-hydroxycrotoamide] has two known mechanisms of action: inhibition of protein kinase activity and inhibition of dihydroorotate dehydrogenase, a key enzyme in the biosynthesis of pyrimidine nucleotide triphosphates.…”

The active metabolite of leflunomide A771726 inhibits corneal neovascularization

“…1 Leflunomide is a new immunosuppressive drug used in the treatment for rheumatoid arthritis. Some organ transplant experimental models revealed that systemic application of leflunomide played strong roles in suppressing allograft rejection [2,3] . Leflunomide exerts anti-inflammatory and immunosuppressive effects via its active metabolite-A771726, which can dissolve liquid easily, whereas leflunomide doesn't.…”