Mycophenolate mofetil (Cellcept).
Mycophenolate mofetil (MMF) is a new immunosuppressive drug designed to inhibit inosine monophosphate dehydrogenase (IMPDH). IMPDH is a key enzyme in the purine synthesis pathway of lymphocytes. IMPDH is crucially important for the proliferative responses of human T- and B-lymphocytes. Therefore, inhibition of IMPDH leads to selective lymphocyte suppression. Following successful testing in different in vitro and animal models, MMF entered clinical trials, where it has been used in combination with cyclosporin and steroids. MMF has rapid and complete absorption following oral administration. Pilot studies suggested a significant reduction in the incidence of rejection at doses of 1-3 g/day. These data led to the initiation of 3 pivotal trials, in which MMF was compared against different standard immunosuppressive protocols. Nearly 1500 patients were enrolled in these 3 randomised, double-blind, multicentre studies of the addition of MMF to standard immunosuppressive protocols for the prevention of acute renal allograft rejection. After six months, the rate of biopsy-proven rejection was significantly reduced. The adverse event profile resembles that of triple therapy with azathioprine: primarily involving the gastrointestinal (GI) tract, the haematopoietic system and the occurrence of opportunistic infections. MMF affords improved immunosuppressive therapy following renal, and probably other solid organ, transplantation. It is licensed for the prevention of acute renal allograft rejection in most countries around the world.
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Abteilung für Abdominal- und Transplantationschirurgie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30623 Hannover, Germany.