Mycophenolate mofetil in organ transplantation: focus on metabolism, safety and tolerability.
Mycophenolate mofetil (MMF) received its first approval for the prevention of renal allograft rejection in 1995 and has now become the most frequently used antiproliferative agent in maintenance immunosuppressive therapy for kidney, pancreas, liver and heart transplantation. In addition, its use for the treatment of autoimmune diseases steadily increases. This review focuses on the miscellaneous pharmacodynamic properties of the drug, its pharmacokinetics in healthy subjects, recipients of different organ transplants and combination therapy with other pharmaceuticals, as well as its safety profile. The immunosuppressive activity of MMF is thought to derive mainly from the potent and selective inhibition of purine synthesis in both T and B lymphocytes. In contrast to other immunosuppressants on the market, it is metabolised primarily by glucuronidation and lacks nephrotoxicity, cardiovascular toxicity or diabetogenic potential, thus making it a suitable candidate for combination regimens. The most important side effects under MMF include gastrointestinal disorders, of which the underlying mechanisms are not yet fully understood, but seem to be complex and related to both effects of mycophenolic acid and its acyl glucuronide, as well as to decreased -immunity due to general immunosuppression after transplantation.
Shipkova
Maria
M
Zentralinstitut für Klinische Chemie and Laboratoriumsmedizin, Klinikum Stuttgart, Kriegsbergstr. 60, D-70174 Stuttgart, Germany. m.shipkova@klinikum-stuttgart.de
Armstrong
Victor William
VW
Oellerich
Michael
M
Wieland
Eberhard
E
D000818:Animals; D004347:Drug Interactions; D018565:Food-Drug Interactions; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D016377:Organ Transplantation; D014181:Transplantation Immunology
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid