Sirolimus in transplantation

Although sirolimus (SRL) alone was very effective in rodents and pigs, it produced toxic side effects in dogs. Low doses of SRL combined with cyclosporine/brequinar (CsA/BQR) combinations achieved potent immunosuppression in the CsA-resistant mouse model. Similarly, SRL/CsA/BQR therapy protected kidney allografts from rejection in dogs without producing toxic side effects. In the CsA-sensitive rat model SRL/CsA combinations produced a potent synergistic interaction. In addition, recent clinical trials document the beneficial effects of low SRL doses in human kidney transplant recipients. Sirolimus, when combined with standard immunosuppressive therapy, remarkably reduces the incidence of acute rejection and permits individual drug dose reduction.