The superior effect of the combination of FK 506 and deoxyspergualin on rat cardiac allograft survival.
In this present study, the effects of FK 506 and 15-deoxyspergualin (DSG), with respect to dose, timing, and combination, were investigated in an ACI-to-LEW rat cardiac allograft model. FK 506 was administered intramuscularly for 14 days starting on day 0 after grafting, while DSG was given intraperitoneally for 7 days starting on day 0,4, or 7 after transplantation. FK 506 or DSG monotherapy prolonged cardiac allograft survival in dose-dependent manners, and the minimum effective dose for overcoming rejection was 0.1 mg/kg per day in the case of FK 506 and 1.0 mg/kg per day for DSG. The graft survival rate was higher with administration of DSG starting on day 4 on day 0 after transplantation. A low dosage of FK 506 starting on day 0, in combination with DSG starting on day 0 or day 4 (but not on day 7), had a synergistic effect in prolonging allograft survival for 14.0 +/- 3.3 days and 25.4 +/- 8.2 days, respectively. The most effective combination treatment schedule for prolongation of allograft survival was FK 506 starting on day 0 and DSG starting on day 4 after transplantation.
Jiang
H
H
Department of Urology, Osaka University Hospital, Japan.
Takahara
S
S
Li
D
D
Namiki
M
M
Ishibashi
M
M
Okuyama
A
A
Sonoda
T
T
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D006085:Graft Survival / Q000187:drug effects*; D006146:Guanidines / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects; D016027:Heart Transplantation / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D007273:Injections, Intramuscular; D007274:Injections, Intraperitoneal; D008297:Male; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D016559:Tacrolimus / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D014184:Transplantation, Homologous
D006146:Guanidines; D007166:Immunosuppressive Agents; C037258:gusperimus; D016559:Tacrolimus