Comparative study analyzing effects of sirolimus-cyclosporin and sirolimus-tacrolimus combinations on bile flow in the rat

The new immunosuppressive agent sirolimus is combined in transplant patient s with the cholestatic substances cyclosporin and tacrolimus. Nothing is kn own about possible cholestatic effects of these combinations. Therefore, we compared their effects on bile flow and on important bile parameters in an acute bile fistula model in rats. Cyclosporin reduced bile flow, biliary e xcretion of bile salts, cholesterol, and GSH to 20-40% of basal values. Sir olimus decreased bile flow to 50% and excretion of GSH to 30% of the initia l conditions but had no effect on cholesterol and bile salt excretion. In c ontrast, tacrolimus increased bile flow to 120% and GSH excretion to 220% o f the basal levels. Sirolimus/cyclosporin decreased bile flow and bile para meters to the same extent as cyclosporin alone. Sirolimus/tacrolimus revers ed sirolimus-induced reduction of bile flow and GSH excretion and resulted in a normal bile salt and cholesterol excretion, thus it may be the better alternative in cholestatic patients.