Sirolimus (Rapamune, rapamycin, Wyeth Pharmaceuticals, Collegeville, PA) is an immunosuppressive drug for renal transplant immunosuppressive therapy. The safety and efficacy of sirolimus in helping prevent tissue rejection was initially demonstrated in two multicenter trials (Trials 301 and 302) involving postrenal transplant patients receiving full-dose cyclosporine and corticosteroids. The data indicated beneficial prophylaxis against
acute rejection from sirolimus therapy in conjunction with cyclosporine and corticosteroids. Subsequently, the safety and efficacy of sirolimus as a maintenance regimen following cyclosporine withdrawal was assessed.
In this study, clinical outcomes of patients withdrawn from cyclosporine and maintained on sirolimus and corticosteroids compared favorably to patients continuing on the triple-drug immunosuppressive regimen. Because of potential toxic effects associated with high trough levels of sirolimus, therapeutic drug monitoring of sirolimus immunosuppressive therapy has been recommended. Pharmacokinetic studies indicate that sirolimus
is primarily sequestered in erythrocytes, and that the appropriate sample medium with which to monitor sirolimus is whole blood.