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  • Title: Mycophenolate mofetil--clinical and experimental experience.
    Author: Pirsch JD, Sollinger HW.
    Journal: Ther Drug Monit; 1996 Aug; 18(4):357-61. PubMed ID: 8857550.
    Abstract:
    Mycophenolate mofetil (MMF) is the first drug approved for the prevention of renal allograft rejection in the United States in the last 10 years. MMF is the morpholinoethyl ester of mycophenolic acid (MPA) and is a selective, reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), an enzyme that is critical for the production of guanine 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 pharmacologically active drug. MPA is highly bound to serum albumin, and recent evidence suggests that the pharmacologic activity of MPA is a function of the unbound drug. Recent studies in human clinical transplantation have demonstrated the efficacy of this compound in renal transplantation. A major clinical study with > 1,499 patients demonstrated a 50% reduction in the incidence of acute rejection when compared with azathioprine or placebo control. The primary side effects in these studies were leukopenia, gastrointestinal problems, and cytomegalovirus disease. MMF represents a major advance in immunosuppression for renal transplant recipients. Ongoing studies are being performed in other types of solid organ transplantation.
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