Cimetidine and omeprazole do not affect cyclosporine disposition by the rat liver

Cyclosporine has been used with increased frequency, occasionally in conjunction with cimetidine and omeprazole. The present study was undertaken to study a possible interaction between either of the two drugs and cyclosporine in the liver. The isolated perfused rat liver was used with recirculation of perfusate for 150 min. 6 experiments were performed with each of the following: cyclosporine alone, cyclosporine with cimetidine, and cyclosporine with omeprazole. Initial concentrations of cyclosporine, cimetidine and omeprazole were 600 micrograms/ml, 12.5 micrograms/ml, and 4.5 micrograms/ml, respectively. At 1 and 2 h of perfusion 1 micrograms of omeprazole was added to perfusate. Cyclosporine concentration was determined at 30 min intervals. Results at 150 min expressed as percentage of the initial concentration of cyclosporine were 59 +/- 3%, 55 +/- 6%, and 60 +/- 9% for cyclosporine alone, with cimetidine and with omeprazole, respectively. The elimination rate of cyclosporine by the liver did not change during the entire experiment with the addition of cimetidine or omeprazole. Thus, it is concluded that short administration of cimetidine or omeprazole will not affect cyclosporine metabolism by the liver.