Mycophenolate mofetil

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Mycophenolate mofetil
Mycophenolate mofetil2DACS.svg
Mycophenolate mofetil ball-and-stick.png
Systematic (IUPAC) name
2-morpholin-4-ylethyl (E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1H-2-benzofuran-5-yl)-4-methylhex-4-enoate
Clinical data
Trade names CellCept
AHFS/Drugs.com monograph
MedlinePlus a601081
Licence data EMA:Link, US FDA:link
Pregnancy cat.
Legal status
Routes Oral, intravenous
Pharmacokinetic data
Bioavailability 94%[1]
Protein binding 82-97%[1]
Metabolism Hepatic[1]
Half-life 17.9±6.5 hours[1]
Excretion Urine (93%), faeces (6%)[1]
Identifiers
ATC code L04AA06
PubChem CID 5281078
DrugBank DB00688
ChemSpider 4444535 YesY
KEGG C07908 YesY
ChEBI CHEBI:8764 N
ChEMBL CHEMBL1456 YesY
Chemical data
Formula C23H31NO7 
Mol. mass 433.49474 g/mol
 N (what is this?)  (verify)

Mycophenolate mofetil (abbreviated MMF, trade name CellCept) is an immunosuppressant and prodrug of mycophenolic acid, used extensively in transplant medicine. It is a reversible inhibitor of inosine monophosphate dehydrogenase[2] (IMPDH) in purine (guanine) biosynthesis which is necessary for the growth of T cells and B cells. Other cells are able to recover purines via a separate salvage pathway and are thus able to escape the effect.

MMF is also used in the treatment of autoimmune diseases, such as Behçet's disease, pemphigus vulgaris, systemic lupus erythematosus and refractory incomplete lupus erythematosus.[3] Suppressing T cells and B cells stops them from attacking healthy cells, but also weakens their ability to defend against infections.

MMF became popular as a less toxic alternative to or in addition to azathioprine and cyclophosphamide.

Adverse effects[edit]

Among the most common side effects of this drug is increased blood cholesterol levels. Other changes in blood chemistry such as hypomagnesemia, hypocalcemia, hyperkalemia, and an increase in BUN are regularly noted. Coughing and issues with breathing are not uncommon - pleural effusions being noted in approximately 1:3. There is a similar occurrence ratio of Infections; with leukopenia and anemia reflecting the immunosuppressive and myelosuppressive nature of the drug. Back and abdominal pain – in addition to headache, nausea, diarrhea, and fever – are also experienced with this drug.

More rarely, various neoplasia occur: melanoma, lymphoma, other malignancies having an occurrences of 1 in 20 to 1 in 200, depending on the type, with Neoplasia in the skin being the most common site.

Other rarer effects include gastrointestinal bleeding and pulmonary fibrosis.

Progressive multifocal leukoencephalopathy is a usually fatal infection of the brain that occurs rarely with this and other immunosuppressive drugs.

Given that this is a pro-drug of mycophenolic acid, the adverse reactions and side-effects noted in that article are also relevant.

Apart from Medscape,[4] the British National Formulary[5] March 2011 was consulted in drafting these side-effects.

Chemistry[edit]

Mycophenolate mofetil is the morpholinoethyl ester of mycophenolic acid; the ester masks the carboxyl group. Mycophenolate mofetil is reported to have a pKa values of 5.6 for the morpholino moiety and 8.5 for the phenolic group.[6]

By comparison, the sodium salt of mycophenolic acid is marketed as Myfortic.

References[edit]

  1. ^ a b c d e "CellCept®" (PDF). TGA eBusiness Services. Roche Products Pty Limited. 13 December 2012. Retrieved 25 February 2014. 
  2. ^ Fulton B, Markham A. "Mycophenolate mofetil : a review of its pharmacodynamic and pharmacokinetic properties and clinical efficacy in renal transplantation." Drugs. 1996, 51(2):278-98.
  3. ^ Boehm I et al. Chilblain lupus erythematosus Hutchinson: successful treatment with mycophenolate mofetil. Arch Dermatol 2001;137:235 – 236 http://archderm.jamanetwork.com/article.aspx?articleid=478189
  4. ^ http://reference.medscape.com/drug/cellcept-myfortic-mycophenolate-343209#4
  5. ^ http://www.bnf.org
  6. ^ http://www.rocheusa.com/products/cellcept/pi.pdf