TY - JOUR
T1 - Mycophenolate mofetil
T2 - An update
AU - Villarroel, Maria Cristina
AU - Hidalgo, Manuel
AU - Jimeno, Antonio
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2009/7
Y1 - 2009/7
N2 - Mycophenolic acid (MPA) is a potent, selective, noncompetitive and reversible inhibitor of inosine-5′-monophosphate deshydrogenase (IMPDH). By depleting guanosine and deoxyguanosine nucleotides in T and B lymphocytes it inhibits their proliferation and, hence, immunoglobin (Ig) production. MPA also suppresses dendritic cell maturation decreasing its capacity of antigen presentation to T lymphocytes. MPA reduces the recruitment of monocytes into sites of graft rejection and inflammation. Mycophenolate mofetil (MMF) is a prodrug of MPA that was developed to improve the bioavailability of MPA. After oral administration, MMF is completely metabolized to MPA. A major inactive metabolite, mycophenolic acid glucuronide (MPAG), is formed after MPA glucuronidation. MPAG has an important role in the enterohepatic recirculation of MPA. MMF is approved for the prophylaxis of allograft rejection after renal, cardiac or liver transplant. The oral dose ranges from 1.0-1.5 g/day twice daily. Moreover, studies on the use of MMF in lung and simultaneous pancreas/kidney transplants have shown encouraging results. MMF also demonstrates potential in the treatment of autoimmune diseases such as lupus, myasthenia gravis and glomerular disorders. This review focuses on the molecular mechanism of action and pharmacological characteristics of MPA. Studies in both approved and non-approved applications are also summarized.
AB - Mycophenolic acid (MPA) is a potent, selective, noncompetitive and reversible inhibitor of inosine-5′-monophosphate deshydrogenase (IMPDH). By depleting guanosine and deoxyguanosine nucleotides in T and B lymphocytes it inhibits their proliferation and, hence, immunoglobin (Ig) production. MPA also suppresses dendritic cell maturation decreasing its capacity of antigen presentation to T lymphocytes. MPA reduces the recruitment of monocytes into sites of graft rejection and inflammation. Mycophenolate mofetil (MMF) is a prodrug of MPA that was developed to improve the bioavailability of MPA. After oral administration, MMF is completely metabolized to MPA. A major inactive metabolite, mycophenolic acid glucuronide (MPAG), is formed after MPA glucuronidation. MPAG has an important role in the enterohepatic recirculation of MPA. MMF is approved for the prophylaxis of allograft rejection after renal, cardiac or liver transplant. The oral dose ranges from 1.0-1.5 g/day twice daily. Moreover, studies on the use of MMF in lung and simultaneous pancreas/kidney transplants have shown encouraging results. MMF also demonstrates potential in the treatment of autoimmune diseases such as lupus, myasthenia gravis and glomerular disorders. This review focuses on the molecular mechanism of action and pharmacological characteristics of MPA. Studies in both approved and non-approved applications are also summarized.
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U2 - 10.1358/dot.2009.45.7.1384878
DO - 10.1358/dot.2009.45.7.1384878
M3 - Review article
C2 - 19834629
AN - SCOPUS:71249141502
SN - 1699-3993
VL - 45
SP - 521
EP - 532
JO - Drugs of Today
JF - Drugs of Today
IS - 7
ER -