A new immunosuppressant, FTY720, in canine kidney transplantation: effect of single-drug, induction and combination treatments.
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.
Suzuki
Tomomi
T
The First Department of Surgery, Hokkaido University School of Medicine, N-15, W-7, Kita-ku, 060-8638 Sapporo, Japan. t-suzu@med.hokudai.ac.jp
Jin
Maeng Bong
MB
Shimamura
Tsuyoshi
T
Yamashita
Kenichiro
K
Taniguchi
Masahiko
M
Nomura
Masaru
M
Yokota
Ryouichi
R
Fukai
Moto
M
Magata
Shinichiro
S
Horiuchi
Hiroyuki
H
Fujita
Miri
M
Nagashima
Kazuro
K
Furukawa
Hiroyuki
H
Todo
Satoru
S
D000818:Animals; D001772:Blood Cell Count; D003331:Coronary Vessels / Q000473:pathology; D016572:Cyclosporine / Q000627:therapeutic use; D004285:Dogs; D004359:Drug Therapy, Combination; D005260:Female; D000068876:Fingolimod Hydrochloride; D006084:Graft Rejection / Q000473:pathology; D006085:Graft Survival / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007422:Intestines / Q000473:pathology; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D016031:Liver Transplantation; D008168:Lung / Q000473:pathology; D011409:Propylene Glycols / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013110:Sphingosine / Q000031:analogs & derivatives; D016019:Survival Analysis; D016559:Tacrolimus / Q000627:therapeutic use
D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D016572:Cyclosporine; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine; D016559:Tacrolimus