THE SYNERGISTIC EFFECT OF BACTOBOLAMINE AND TACROLIMUS ON IN-VITRO AND IN-VIVO EXPERIMENTS

The aim of this study was to examine the immunosuppressive effect of b actobolamine (BBL) alone and in combination with tacrolimus (FK) using in vitro proliferation assays on human peripheral blood lymphocytes ( PBL) and in vivo liver allografts in rats. In the latter setting, the immunosuppressive activity of BBL alone and in combination with FK was compared to that of mizoribine (MIZ). The interactions between BBL an d FK and between MIZ and FK were assessed by the combination index (CI ) proposed by Chou and Kahan. In the in vitro study, the combination o f BBL and FK displayed stronger inhibitory effects on T-cell prolifera tion than when each drug was applied alone. The mean CI values fro the BBL/FK combination were below 1.0, ranging from 0.19 to 0.86, indicat ing synergism between BBL and FK. In the in vivo study, 50-200 mg/kg/d ay BBL monotherapy significantly prolonged survival compared with a co ntrol group, and the effect was dose-dependent. Conversely, the effica cy of MIZ monotherapy at 2.5-10 mg/kg/day did not increase dose-depend ently. The CIs for MIZ at doses of 2.5 and 5.0 mg/kg/day with FK 0.08 mg/kg/day were 0.48 and 0.42, respectively, indicating therapeutic syn ergism between MIZ and FK. The CI for BBL 100 mg/kg/day with FK was 0. 26, which indicated further synergism between BBL and FK.