An immunosuppressive regimen using FTY720 combined with cyclosporin in canine kidney transplantation.
FTY720 induces apoptosis, specifically in lymphocytes, and prolongs allograft survival in rats and dogs. The purpose of this study was to define an effective range of FTY720 doses that could be combined with a suboptimal dose (10 mg/kg) of cyclosporin for canine kidney allograft recipients. The combination significantly prolonged allograft survival in all groups receiving FTY720 at a dose of 0.1, 0.3, 1.0, or 3.0 mg/kg. None of the recipients died due to notable side effects of the drug. In peripheral blood, the number of lymphocytes was extremely low, whereas the percentage of granulocytes increased during FTY720 administration. No significant difference in cyclosporin trough levels was observed between the cyclosporin-alone group and the combination groups. We conclude from the present study that FTY720 has a potent effect at an extremely low dose and a wide therapeutic window when combined with cyclosporin in canine kidney transplants.
Suzuki
S
S
Department of Experimental Surgery and Bioengineering, National Children's Medical Research Center, Tokyo, Japan. ssuzuki@nch.go.jp
Kakefuda
T
T
Amemiya
H
H
Chiba
K
K
Hoshino
Y
Y
Kawaguchi
T
T
Kataoka
H
H
Rahman
F
F
D000818:Animals; D016572:Cyclosporine / Q000627:therapeutic use*; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D000068876:Fingolimod Hydrochloride; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000517:prevention & control*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation; D007958:Leukocyte Count / Q000187:drug effects; D011409:Propylene Glycols / Q000627:therapeutic use*; D013110:Sphingosine / Q000031:analogs & derivatives
D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D016572:Cyclosporine; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine