Mycophenolic acid

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Mycophenolic acid
Systematic (IUPAC) name
(E)-6-(4-hydroxy-6-methoxy-7-methyl- 3-oxo-1,3-dihydroisobenzofuran-5-yl)- 4-methylhex-4-enoic acid
Identifiers
CAS number	24280-93-1
ATC code	L04AA06
PubChem	446541
Chemical data
Formula	C₁₇H₂₀O₆
Mol. mass	320.34 g.mol^-1
Pharmacokinetic data
Bioavailability	94% (mofetil), 72% (sodium)
Protein binding	97%
Metabolism	Hepatic
Half life	16–18 hours
Excretion	Renal 93%
Therapeutic considerations
Licence data	EU US
Pregnancy cat.	D (Au), C (U.S.)
Legal status	S4 (Au), POM (UK), ℞-only (U.S.)
Routes	Oral, IV

Mycophenolic acid (INN) (IPA: [ˌmaɪkoˈfɛnɒlɪk- ]) or mycophenolate is an immunosuppressant drug used to prevent rejection in organ transplantation. It was initially marketed as the prodrug mycophenolate mofetil (abbreviated MMF) to improve oral bioavailability. More recently, the salt mycophenolate sodium has also been introduced. Mycophenolic acid is commonly marketed under the trade names CellCept (mycophenolate mofetil; Roche) and Myfortic (mycophenolate sodium; Novartis).

1 Pharmacokinetics/pharmacology
2 Clinical use
3 Footnotes
4 External links

[edit] Pharmacokinetics/pharmacology

Mycophenolate is derived from the fungus Penicillium stoloniferum. Mycophenolate mofetil is metabolised in the liver to the active moiety mycophenolic acid. It inhibits inosine monophosphate dehydrogenase, the enzyme which controls the rate of synthesis of guanine monophosphate in the de novo pathway of purine synthesis used in the proliferation of B and T lymphocytes.

Mycophenolate is potent and can be used in place of the older anti-proliferative azathioprine. It is usually used as part of triple-therapy including a calcineurin inhibitor (cyclosporin or tacrolimus) and prednisolone.

[edit] Clinical use

[edit] Indications

Generally speaking, mycophenolate is used for the prevention of organ transplant rejection. Specifically, mycophenolate mofetil is indicated for the prevention of organ transplant rejection in adults and renal transplant rejection in children >2 years; while mycophenolate sodium is indicated for the prevention of renal transplant rejection in adults. Mycophenolate sodium has also been used for the prevention of rejection in liver, heart and/or lung transplants in children >2 years.^[1]

Recently, several studies have shown that oral mycophenolate mofetil is effective in inducing and maintaining remission in lupus nephritis.^[2] It has been shown to be more effective and have fewer adverse effects than intravenous cyclophosphamide for lupus nephritis and has has now become accepted first-line treatment for this disorder.

[edit] Adverse effects

Common adverse drug reactions (≥1% of patients) associated with mycophenolate therapy include: diarrhea, nausea, vomiting, infections, leukopenia, and/or anemia. Mycophenolate sodium is also commonly associated with fatigue, headache and/or cough. Intravenous (IV) administration of mycophenolate mofetil is also commonly associated with thrombophlebitis and thrombosis. Infrequent adverse effects (0.1–1% of patients) include: esophagitis, gastritis, gastrointestinal tract hemorrhage, and/or invasive cytomegalovirus (CMV) infection.^[1]

[edit] Comparison to other agents

Compared with azathioprine it is more lymphocyte-specific and is associated with less bone marrow suppression, fewer opportunistic infections and lower incidence of acute rejection.^[3] The exact role of mycophenolate vs azathioprine has yet to be conclusively established, but many centers use it in place of azathioprine for high-risk patients, or patients who have already experienced an episode of acute rejection. In long-term immunosuppression, it may be used to avoid calcineurin inhibitors or steroids.

[edit] Potential future uses

Mycophenolate mofetil is beginning to be used in the management of idiopathic thrombocytopenic purpura (ITP) and systemic lupus erythematosus (SLE) with success for some patients.

It is also currently being used as a long term therapy for maintaining remission of Wegener's Granulomatosis.

[edit] Footnotes

^ ^a ^b Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3
^ Ginzler EM, Dooley MA, Aranow C, Kim MY, et al. "Mycophenolate Mofetil or Intravenous Cyclophosphamide for Lupus Nephritis." New England Journal of Medicine. 353:21. 2219-2229. 24 November 2005.
^ Woodroffe R, Yao G, Meads C, Bayliss S, Ready A, Raftery J, et al. Clinical and cost-effectiveness of newer immunosuppressive regimens in renal transplantation: a systematic review and modelling study. Health Technol Assess 2005;9(21):1-194. PMID 15899149