Mycophenolate mofetil: suggested guidelines for use in kidney transplantation

Mycophenolate mofetil (MMF) is an immunosuppressive drug designed to inhibit inosine monophosphate dehydrogenase (IMPDH). IMPDH is a key enzyme in the de novo purine synthesis of lymphocytes. It is crucially important for proliferative responses of human T and B lymphocytes. The inhibition of IMPDH thus leads to selective lymphocyte suppression. After successful use in various in vitro and animal models, MMF was brought to clinical trial in patients undergoing transplantation. The drug is rapidly and completely absorbed following oral administration. Pilot studies of administration with cyclosporin and corticosteroids suggested a significant reduction in the incidence of organ rejection at dosages of 1 to 3 g/day. As a result of these studies, 3 pivotal randomised double-blind multicentre trials, involving nearly 1500 patients, were designed to investigate the effects of addition of MMF to different standard immunosuppressive protocols on the prevention of acute renal allograft rejection. After 6 months, the rates of biopsy-proven rejection were significantly reduced in patients receiving MMF. In combination with cyclosporin and corticosteroids, the adverse effect profile resembled that of azathioprine. Most adverse effects were associated with the gastrointestinal tract, the blood system and opportunistic infections. MMF offers improved immunosuppressive therapy following renal and probably other solid organ transplantation. MMF has been licensed since 1995 for the prevention of acute renal allograft rejection in most countries. It has been used in different combinations of immunosuppressive drugs and in various dosages and regimens.