Mycophenolate mofetil: a unique immunosuppressive agent.

Abstract

The mechanism of action, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of mycophenolate mofetil are reviewed. Mycophenolate mofetil is used to prevent or treat allograft rejection after solid-organ transplantation. A prodrug, mycophenolate mofetil is rapidly hydrolyzed to mycophenolic acid after oral administration. Mycophenolic acid inhibits de novo purine synthesis, resulting in antiproliferative effects on T and B lymphocytes. The absolute bioavailability of mycophenolic acid is 94% for oral administration; the maximum plasma concentration occurs after two hours. Mycophenolic acid undergoes hepatic glucuronidation to an inactive salt that is renally excreted. Clinical trials of mycophenolate mofetil in renal transplant patients suggest that the drug is effective for the prevention of acute rejection and as rescue therapy. Clinical data on mycophenolate mofetil therapy in liver transplant patients are too limited to permit conclusions. Clinical trials of the drug for primary immunosuppression in heart transplant patients have not been conducted, but studies of this agent as rescue therapy suggest efficacy. Mycophenolic acid has proved useful for long-term management of psoriasis. The most common adverse effects of mycophenolate mofetil are gastrointestinal. Nephrotoxicity and overt hepatotoxicity have not been reported, but the drug may be linked to bone marrow suppression and certain malignancies. Mycophenolate mofetil is available as a 250-mg capsule for oral use. The recommended initial dosage is 1 g twice daily. Mycophenolate mofetil appears to be a useful addition to the armamentarium of immunosuppressive drugs, particularly for kidney transplant patients, but more study is needed to clarify its role.