Mycophenolic acid

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Mycophenolate
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Mycophenolic acid
Clinical data
Pronunciation/ˌmaɪkoʊfɪˈnɒlɪk/
Trade namesCellcept, Myfortic, others
Other namesMPA, Mycophenolate sodium, Mycophenolate mofetil (AAN AU), Mycophenolate mofetil (USAN US)
AHFS/Drugs.comMonograph
MedlinePlusa601081
License data
Pregnancy
category
intravenous[2]
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability72% (sodium),
94% (mofetil)[10]
Protein binding82–97%[10]
MetabolismLiver[10]
Elimination half-life17.9±6.5 hours[10]
ExcretionUrine (93%),
faeces (6%)[10]
Identifiers
  • (4E)-6-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoic acid
JSmol)
  • O=C1OCc2c1c(O)c(c(OC)c2C)C\C=C(/C)CCC(=O)O
  • InChI=1S/C17H20O6/c1-9(5-7-13(18)19)4-6-11-15(20)14-12(8-23-17(14)21)10(2)16(11)22-3/h4,20H,5-8H2,1-3H3,(H,18,19)/b9-4+ checkY
  • Key:HPNSFSBZBAHARI-RUDMXATFSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Mycophenolic acid is an

heart, and liver transplantation.[12] It can be given by mouth or by injection into a vein.[12] It comes as mycophenolate sodium and mycophenolate mofetil.[12]

Common side effects include nausea, infections, and diarrhea.

lymphocytes to make guanosine.[12]

Mycophenolic acid was initially discovered by Italian

generic medication.[15] In 2020, it was the 313th most commonly prescribed medication in the United States, with more than 900 thousand prescriptions.[16]

Medical uses

Organ transplant

Mycophenolate is used for the prevention of

organ transplant rejection. Mycophenolate mofetil is indicated for the prevention of organ transplant rejection in adults and kidney transplantation rejection in children over 2 years; whereas mycophenolate sodium is indicated for the prevention of kidney transplant rejection in adults. Mycophenolate sodium has also been used for the prevention of rejection in liver, heart, or lung transplants in children older than two years.[17]

Autoimmune disease

Mycophenolate is increasingly utilized as a steroid sparing treatment in

vasculitides, and psoriasis.[18] It is also used for retroperitoneal fibrosis along with a number of other medications.[19] Specifically it has also be used for psoriasis not treatable by other methods.[20]

Its increasing application in treating lupus nephritis has demonstrated more frequent complete response and less frequent complications[18] compared to cyclophosphamide bolus therapy, a regimen with risk of bone marrow suppression, infertility, and malignancy.[11] Further work addressing maintenance therapy demonstrated mycophenolate superior to cyclophosphamide, again in terms of response and side-effects.[11][21] Walsh proposed that mycophenolate should be considered as a first-line induction therapy for treatment of lupus nephritis in people without kidney dysfunction.[22]

Comparison to other agents

Compared with azathioprine it has higher incidence of diarrhea, and no difference in risk of any of the other side effects in transplant patients.[23] Mycophenolic acid is 15 times more expensive than azathioprine.[24]

Adverse effects

Common

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.[25][26][not specific enough to verify
] Several cases of pure red cell aplasia (PRCA) have also been reported.[27]

The U.S.

viral infection known as progressive multifocal leukoencephalopathy; it attacks the brain and is usually fatal.[28]

Pregnancy

Mycophenolic acid is associated with miscarriage and congenital malformations when used during pregnancy, and should be avoided whenever possible by women trying to get pregnant.[29][30]

Blood tests

Among the most common effects of this drug is increased blood cholesterol levels. Other changes in blood chemistry such as

hypomagnesemia, hypocalcemia, hyperkalemia, and an increase in blood urea nitrogen (BUN) can occur.[2][31]

Mechanism of action

Purines (including the nucleosides

B cells
.

Pharmacology

Mycophenolate can be derived from the fungi

lymphocytes.[37] Other cells recover purines via a separate salvage pathway and are thus able to escape the effect.[2]

Mycophenolate is potent and can, in many contexts, be used in place of the older anti-proliferative azathioprine.[38] It is usually used as part of a three-compound regimen of immunosuppressants, also including a calcineurin inhibitor (ciclosporin or tacrolimus) and a glucocorticoid (e.g. dexamethasone or prednisone).[39]

Chemistry

Mycophenolate mofetil, a prodrug form of mycophenolic acid used in medicine

Mycophenolate mofetil is the

pKa
values of 5.6 for the morpholino moiety and 8.5 for the phenolic group.

History

Mycophenolic acid was discovered by Italian medical scientist

Roche) and Myfortic (mycophenolate sodium by Novartis).[43]

Cellcept was developed by a South African geneticist

U.S. Food and Drug Administration on 3 May 1995,[55] and was sold under the brand name CellCept.[56][57] It was approved for use in the European Union in February 1996.[9]

Names

It was initially introduced as the prodrug mycophenolate mofetil (MMF, trade name CellCept) to improve oral bioavailability. The salt mycophenolate sodium has also been introduced. Enteric-coated mycophenolate sodium (EC-MPS) is an alternative MPA formulation.

MMF and EC-MPS appear to be equal in benefits and safety.[58]

Research

Mycophenolate mofetil is beginning to be used in the management of auto-immune disorders such as

systemic lupus erythematosus (SLE), scleroderma (systemic sclerosis or SSc), and pemphigus vulgaris (PV) with success for some patients.[59]

It is also currently being used as a long-term therapy for maintaining remission of

MERS, especially in combination with interferon.[62]

Preliminary data suggests that

mycophenolate mofetil might have benefits in people with multiple sclerosis. However the evidence is insufficient to determine the effects as an add‐on therapy for interferon beta-1a in people with RRMS.[63]

References

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