A new immunosuppressant, FTY720, in canine kidney transplantation: effect of single-drug, induction and combination treatments

• Published in: Transplant international 2004-11, Vol.17 (10), p.574
• Main Authors: Suzuki, Tomomi, Maeng, Bong Jin, Shimamura, Tsuyoshi, Yamashita, Kenichiro, Taniguchi, Masahiko, Nomura, Masaru, Yokota, Ryouichi, Fukai, Moto, Magata, Shinichiro, Horiuchi, Hiroyuki, Fujita, Miri, Nagashima, Kazuro, Furukawa, Hiroyuki, Todo, Satoru
• Format: Article
• Language: English
• ISSN: 0934-0874; 1432-2277
• DOI: 10.1007/s00147-004-0767-7

Three different types of treatment were conducted to clarify the properties of a novel immunomodulator, FTY720, in canine kidney allograft models. Survival, biochemical and hematological tests, pharmacokinetics, and histopathology of grafts and extra-renal organs were analyzed. Accompanying a remarkable reduction in circulating lymphocytes, single-drug treatment of FTY720, ranging from 0.05 to 10 mg/kg, exhibited significant prolongation of graft survival without a dose-dependent effect. Short-course induction with FTY720 at 5 mg/kg per day exhibited similar anti-rejection effects as did single-drug treatment but no advantage in rescuing ongoing rejection. In combination with cyclosporine (CsA; 5 mg/kg) or tacrolimus (FK; 0.5 mg/kg), FTY720 had an additive effect. Trough blood concentrations of FTY720 were linearly correlated with dose. No animal showed critical adverse effects at any point. FTY720 holds promise as a candidate in a new category of drugs that can be combined with conventional agents for induction and maintenance immunosuppression in clinical organ transplantation.