MYCOPHENOLATE MOFETIL - CLINICAL AND EXPERIMENTAL EXPERIENCE

Mycophenolate mofetil (MMF) is the first drug approved for the prevent ion of renal allograft rejection in the United States in the last 10 y ears. MMF is the morpholinoethyl ester of mycophenolic acid (MPA) and is a selective, reversible inhibitor of inosine monophosphate dehydrog enase (IMPDH), an enzyme that is critical for the production of guanin e monophosphate. MPA is a potent inhibitor of IMPDH, particularly the type II isoform. Compared with other cell types, lymphocytes appear to be more sensitive to inhibition of the type II isoform of IMPDH. This decreases the metabolism of guanine nucleotides, which are necessary for cell function. MMF is rapidly converted to MPA, which is the pharm acologically active drug. MPA is highly bound to serum albumin, and re cent evidence suggests that the pharmacologic activity of MPA is a fun ction of the unbound drug. Recent studies in human clinical transplant ation have demonstrated the efficacy of this compound in renal transpl antation. A major clinical study with >1,499 patients demonstrated a 5 0% reduction in the incidence of acute rejection when compared with az athioprine or placebo control. The primary side effects in these studi es were leukopenia, gastrointestinal problems, and cytomegalovirus dis ease. MMF represents a major advance in immunosuppression for renal tr ansplant recipients. Ongoing studies are being performed in other type s of solid organ transplantation.