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 allotransplan tation of the left lung. The experimental animals were allocated to si x 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, cyc losporine 20 mg/kg/day, by mouth); group C (n = 5, FK-506 0.03 mg/kg/d ay, intramuscularly); group D (n = 5, cyclosporine 6 mg/kg/day, by mou th); 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/d ay). The animals were killed on postoperative day 28 or when extreme d eterioration had developed. In groups C and D, the grafts underwent mo derate to severe rejection. The treatment in group E resulted in insuf ficient immunosuppression, although additional effect was noted. The r ejection 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 n ot 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.