[Mycophenolate mofetil--a new immunosuppressive agent].
Stein Bergan, D Albrechtsen, Per Fauchald
Abstract
Stein Bergan, D Albrechtsen, Per Fauchald
Abstract
Mycophenolate mofetil is a prodrug that is rapidly converted to the active immunosuppressant mycophenolic acid. This substance inhibits the enzyme inosine monophosphate dehydrogenase, leading to a depletion of (deoxy-)guanosine nucleotides and thereby a reduction of de novo purine synthesis. Lymphocytes are relatively dependent on this pathway, particularly for RNA and DNA synthesis, and are thereby more susceptible to the antiproliferative effects of mycophenolate. In three randomised, double-blind, multicentre trials, lower rejection rates have been demonstrated in renal allograft recipients during the first months after transplantation. Side effects were more frequent in the mycophenolate mofetil groups. The most important adverse reactions to mycophenolate mofetil are leucopenia, gastrointestinal effects and the increased risk of infections and malignancies associated with immunosuppression in general. At 12 months, graft survival was similar in all groups. The future role of mycophenolate mofetil in immunosuppressive therapy during transplantation has not yet been established. As a start it may be found to have specific use in subgroups of allograft recipients at high risk of rejection.
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Mycophenolate mofetil is a prodrug that is rapidly converted to the active immunosuppressant mycophenolic acid. This substance inhibits the enzyme inosine monophosphate dehydrogenase, leading to a depletion of (deoxy-)guanosine nucleotides and thereby a reduction of de novo purine synthesis. Lymphocytes are relatively dependent on this pathway, particularly for RNA and DNA synthesis, and are thereby more susceptible to the antiproliferative effects of mycophenolate. In three randomised, double-blind, multicentre trials, lower rejection rates have been demonstrated in renal allograft recipients during the first months after transplantation. Side effects were more frequent in the mycophenolate mofetil groups. The most important adverse reactions to mycophenolate mofetil are leucopenia, gastrointestinal effects and the increased risk of infections and malignancies associated with immunosuppression in general. At 12 months, graft survival was similar in all groups. The future role of mycophenolate mofetil in immunosuppressive therapy during transplantation has not yet been established. As a start it may be found to have specific use in subgroups of allograft recipients at high risk of rejection.
Key concepts: Mycophenolate, Mycophenolic acid, IMP dehydrogenase, Immunosuppression, Medicine, Pharmacology, Prodrug, Transplantation