Combined therapy with FK-506 and cyclosporine for canine lung allotransplantation: immunosuppressive effects and blood trough levels.
The therapeutic and adverse effects of FK-506 and cyclosporine used in combination were examined in 35 adult mongrel dogs with allotransplantation of the left lung. The experimental animals were allocated to six groups: group A, optimal dose of FK-506 (n = 5, FK-506 0.1 mg/kg/day, intramuscularly); group B, optimal dose of cyclosporine, (n = 5, cyclosporine 20 mg/kg/day, by mouth); group C (n = 5, FK-506 0.03 mg/kg/day, intramuscularly); group D (n = 5, cyclosporine 6 mg/kg/day, by mouth); group E (n = 5, FK-506 0.03 mg/kg/day+cyclosporine 6 mg/kg/day); and group F (n = 10, FK-506 0.05 mg/kg/day+cyclosporine 10 mg/kg/day). The animals were killed on postoperative day 28 or when extreme deterioration had developed. In groups C and D, the grafts underwent moderate to severe rejection. The treatment in group E resulted in insufficient immunosuppression, although additional effect was noted. The rejection was suppressed at least as strongly in group F as in groups A and B. One death occurred in each of groups A and F from hematemesis. The blood concentrations of FK-506 and cyclosporine in group E were not higher than in groups C and D. The whole blood concentrations of FK-506 deviated less, and they were superior to the serum concentrations as a monitor. The combination of FK-506 and cyclosporine at one half of their optimal doses suppressed the rejection almost completely and did not increase the adverse effects.
Fukuse
T
T
Department of Thoracic Surgery, Kyoto University, Japan.
Hirai
T
T
Yokomise
H
H
Hasegawa
S
S
Hirata
T
T
Muro
K
K
Inui
K
K
Hitomi
S
S
Wada
H
H
D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D004285:Dogs; D004359:Drug Therapy, Combination; D006084:Graft Rejection; D007165:Immunosuppression Therapy; D016040:Lung Transplantation; D016559:Tacrolimus / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity
D016572:Cyclosporine; D016559:Tacrolimus