Mycophenolate mofetil in solid-organ transplantation

Titte R. Srinivas, Bruce Kaplan, Herwig Ulf Meier-Kriesche

    Research output: Contribution to journalReview articlepeer-review

    55 Scopus citations

    Abstract

    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.

    Original languageEnglish (US)
    Pages (from-to)2325-2345
    Number of pages21
    JournalExpert Opinion on Pharmacotherapy
    Volume4
    Issue number12
    DOIs
    StatePublished - Dec 1 2003

    Keywords

    • Mycophenolate mofetil
    • Mycophenolic acid
    • Transplantation

    ASJC Scopus subject areas

    • Pharmacology
    • Pharmacology (medical)

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