MYCOPHENOLATE MOFETIL - A REVIEW OF ITS PHARMACODYNAMIC AND PHARMACOKINETIC PROPERTIES AND CLINICAL EFFICACY IN RENAL-TRANSPLANTATION

Mycophenolate mofetil is an ester prodrug of the active immunosuppuess ant mycophenolic acid. It is a noncompetitive, selective and reversibl e inhibitor of inosine monophosphate dehydrogenase, an important enzym e in the de novo synthesis of guanosine nucleotides in T and B lymphoc ytes. Mycophenolate mofetil and/or mycophenolic acid inhibit the proli feration of lymphocytes and the production of antibodies induced by a variety of mitogens and antigens. Mycophenolate mofetil is also active in several animal models of transplantation and has produced effects in animals that indicate that it may inhibit the chronic rejection pro cess. Mycophenolate mofetil has been compared with azathioprine or pla cebo in 3 large, randomised, double-blind, multicentre trials as part of combination immunosuppression therapy wish cyclosporin and corticos teroids. Compared with either placebo or azathioprine (1 to 2 mg/kg/da y or 100 to 150 mg/day), mycophenolate mofetil 2 or 3 g/day was associ ated with a significantly lower proportion of patients experiencing ac ute rejection or treatment failure during the first 6 months after tra nsplantation. Mycophenolate mofetil also tended to be associated with a lower proportion of patients who required a full course of antirejec tion therapy However the proportion of patients who died or who had gr aft loss was similar between all of the treatment groups. There are cu rrently no data regarding the effects of mycophenolate mofetil on long term patient or graft survival, which are important clinical outcomes in assessing its place in the management of renal transplantation. Cl inical trials ave also needed to evaluate mycophenolate mofetil in spe cific patient populations (e.g. repeat renal transplant patients or hi ghly sensitised patients), to determine its efficacy in alternative im munosuppressive protocols and to investigate its use in the transplant ation of other solid organs. In summary, mycophenolate mofetil appears to be an attractive new agent in the prevention of graft rejection in renal transplant recipients that has shown superior efficacy to azath ioprine. Although long term clinical outcome data are required, mycoph enolate is a potentially important advance in transplant immunosuppres sion.