Mycophenolate mofetil in solid-organ transplantation.
This review focuses on the use of mycophenolate mofetil (MMF) as an immunosuppressive agent in solid-organ transplantation. MMF, a non-competitive inhibitor of inosine monophosphate dehydrogenase, blocks de novo purine synthesis in T and B lymphocytes, resulting in the selective inhibition of proliferation of these cells in response to antigenic stimuli. MMF may also promote apoptosis of these cells. The immunosuppressive ability of MMF is thought to derive mainly from the inhibition of inosine monophosphate dehydrogenase. The other effects of MMF include suppression of antibody synthesis by B lymphocytes, inhibition of proliferation of smooth muscle cells in culture and impaired glycosylation of adhesion molecules. MMF may exhibit anti-inflammatory effects resulting from decreased activity of the inducible form of nitric oxide synthase, a consequence of depletion of tetrahydrobiopterin, which leads to decreased generation of peroxynitrite, a pro-inflammatory molecule. The pharmacokinetics, pharmacodynamics and principles underlying therapeutic drug monitoring of MMF are reviewed. The results of the pivotal clinical trials of MMF in kidney and heart transplantation are discussed and a summary of the major studies demonstrating a positive effect of MMF on renal transplantation outcomes is presented. The use of MMF in the context of ABO-incompatible renal transplantation, renal transplantation in highly sensitised and cross-match positive recipients, humoral rejection of renal allografts, chronic allograft nephropathy and steroid/calcineurin inhibitor minimisation in renal transplantation are also discussed.
Srinivas
Titte R
TR
Division of Nephrology, Hypertension and Transplantation, University of Florida, 1600 SW Archer Road, Box 100224, Gainesville, FL 32610-0224, USA.
Kaplan
Bruce
B
Meier-Kriesche
Herwig Ulf
HU
D000818:Animals; D002908:Chronic Disease; D002986:Clinical Trials as Topic; D004347:Drug Interactions; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016377:Organ Transplantation; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid