A review of clinical experience with the novel immunosuppressive drug mycophenolate mofetil in renal transplantation.

This review gives a summary about the current knowledge on the novel immunosuppressive drug mycophenolate mofetil (RS61443) in renal transplantation. The results of the preclinical pilot trials and of the so far published pivotal study for the prevention of rejection are described. Mycophenolate mofetil (MMF), the 2-4-morpholino ethyl ester of mycophenolic acid, is an inhibitor of the Inosine Monophosphate Dehydrogenase, an enzyme in the de novo synthesis of purines. MMF showed no clinical significant interactions with a variety of medications used in renal transplantation. Following oral administration it is rapidly absorbed. Pilot studied suggested a significant reduction in the incidence of rejection at doses of 2 g/day. 491 patients were enrolled in a randomized, double blind, multicentre, placebo-controlled study of the addition of mycophenolate mofetil to cyclosporine and oral corticosteroids for the prevention of acute renal allograft rejection. After six month the rates for biopsy proven rejection were the following: placebo 46.4%, MMF 2 g 17.0% and MMF 3 g 13.8%. The adverse event profile resembles that of triple therapy with azathioprine. Most adverse events concerned the gastrointestinal tract, the hemic system and opportunistic infections. MMF offers an improved immunosuppressive therapy following renal transplantation.