MYCOPHENOLATE MOFETIL

Mycophenolate mofetil (MMF), the morpholinoethyl ester of mycophenolic acid (MPA), is a new selective immunosuppressant used for the prevent ion and treatment of acute renal rejection after transplantation. In v ivo MMF is deesterified to MPA, which is a potent and specific inhibit or of de novo purine synthesis and suppressor of both T and B lymphocy te proliferation. In animal studies, MMF has been shown to be effectiv e in prolonging the survival of allografts and xenografts in rodents, dogs, and monkeys. Experimental evidence in animal models suggests tha t MMF also may be effective in the treatment of chronic vascular rejec tion. A phase I clinical trial showed MMF was well tolerated in renal transplant patients at doses up to 3,500 mg/day for up to two years. T here was no correlation between the incidence of adverse effects and d ose of MMF, and no overt nephrotoxicity, hepatotoxicity, or myelotoxic ity was observed. In a multicenter study in patients with biopsy-prove n renal allograft rejection, successful rescue (stabilization or impro vement of renal function) was achieved with MMF in combination with ma intenance doses of cyclosporine and prednisone in 69% of patients. Thi s result suggested that MMF may be effective in the treatment of renal allograft rejection after transplantation. In a large multicenter tri al, MMF in combination with cyclosporine and prednisone was superior t o a standard immunosuppressive regimen including azathioprine. Taken t ogether, the data indicate that MMF will be a valuable addition to the list of immunosuppressants available for the prevention and treatment of renal rejection after transplantation.