Mycophenolic acid explained

Verifiedfields:changed
Watchedfields:changed
Verifiedrevid:476995047
Width:200
Aan:Mycophenolate mofetil
Usan:Mycophenolate mofetil
Tradename:Cellcept, Myfortic, Myhibbin, others
Dailymedid:Mycophenolate mofetil
Pregnancy Au:D
Pregnancy Au Comment:[1]
Routes Of Administration:By mouth, intravenous
Atc Prefix:L04
Atc Suffix:AA06
Legal Au:S4
Legal Au Comment:[2] [3]
Legal Ca:Rx-only
Legal Uk:POM
Legal Uk Comment:[4] [5] [6]
Legal Us:Rx-only
Legal Us Comment:[7] [8]
Legal Eu:Rx-only
Legal Status:Rx-only
Bioavailability:72% (sodium),
94% (mofetil)[9]
Protein Bound:82–97%
Metabolism:Liver
Elimination Half-Life:17.9±6.5 hours
Excretion:Urine (93%),
faeces (6%)
Cas Number:24280-93-1
Pubchem:446541
Iuphar Ligand:6832
Drugbank:DB01024
Chemspiderid:393865
Unii:HU9DX48N0T
Kegg:D05096
Chebi:168396
Chembl:866
Synonyms:MPA, Mycophenolate sodium
Iupac Name:(4E)-6-(4-Hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methylhex-4-enoic acid
C:17
H:20
O:6
Smiles:O=C1OCc2c1c(O)c(c(OC)c2C)C\C=C(/C)CCC(=O)O
Stdinchi: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+
Stdinchikey:HPNSFSBZBAHARI-RUDMXATFSA-N

Mycophenolic acid is an immunosuppressant medication used to prevent rejection following organ transplantation and to treat autoimmune conditions such as Crohn's disease and lupus. Specifically it is used following kidney, heart, and liver transplantation. It can be given by mouth or by injection into a vein. It comes as mycophenolate sodium and mycophenolate mofetil.

Common side effects include nausea, infections, and diarrhea. Other serious side effects include an increased risk of cancer, progressive multifocal leukoencephalopathy, anemia, and gastrointestinal bleeding. Use during pregnancy may harm the baby. It works by blocking inosine monophosphate dehydrogenase (IMPDH), which is needed by lymphocytes to make guanosine.

Mycophenolic acid was initially discovered by Italian Bartolomeo Gosio in 1893.[10] [11] It was rediscovered in 1945 and 1968.[11] It was approved for medical use in the United States in 1995 following the discovery of its immunosuppressive properties in the 1990s.[12] [10] It is available as a generic medication.[13] In 2020, it was the 313th most commonly prescribed medication in the United States, with more than 900thousand prescriptions.[14]

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.[15]

Autoimmune disease

Mycophenolate is increasingly utilized as a steroid sparing treatment in autoimmune diseases and similar immune-mediated disorders including Behçet's disease, pemphigus vulgaris, immunoglobulin A nephropathy, small vessel vasculitides, and psoriasis.[16] It is also used for retroperitoneal fibrosis along with a number of other medications.[17] Specifically it has also be used for psoriasis not treatable by other methods.[18]

Its increasing application in treating lupus nephritis has demonstrated more frequent complete response and less frequent complications[16] compared to cyclophosphamide bolus therapy, a regimen with risk of bone marrow suppression, infertility, and malignancy.[19] Further work addressing maintenance therapy demonstrated mycophenolate superior to cyclophosphamide, again in terms of response and side-effects.[19] [20] Walsh proposed that mycophenolate should be considered as a first-line induction therapy for treatment of lupus nephritis in people without kidney dysfunction.[21]

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.[22] Mycophenolic acid is 15 times more expensive than azathioprine.[23]

Adverse effects

Common adverse drug reactions (≥ 1% of people) include diarrhea, nausea, vomiting, joint pain; infections, leukopenia, or anemia reflect the immunosuppressive and myelosuppressive nature of the drug. Mycophenolate sodium is also commonly associated with fatigue, headache, cough and/or breathing issues. Intravenous (IV) administration of mycophenolate mofetil is also commonly associated with thrombophlebitis and thrombosis. Infrequent adverse effects (0.1–1% of people) include esophagitis, gastritis, gastrointestinal tract hemorrhage, and/or invasive cytomegalovirus (CMV) infection.[15] More rarely, pulmonary fibrosis or 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.[24] [25] Several cases of pure red cell aplasia (PRCA) have also been reported.[26]

The U.S. Food and Drug Administration (FDA) issued an alert that people are at increased risk of opportunistic infections, such as activation of latent viral infections, including shingles, other herpes infections, cytomegalovirus, and BK virus associated nephropathy. In addition the FDA is investigating 16 people that developed a rare neurological disease while taking the drug. This is a viral infection known as progressive multifocal leukoencephalopathy; it attacks the brain and is usually fatal.[27]

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.[28] [29]

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.[30] [31]

Mechanism of action

Purines (including the nucleosides guanosine and adenosine) can either be synthesized de novo using ribose 5-phosphate or they can be salvaged from free nucleotides. Mycophenolic acid is a potent, reversible, non-competitive inhibitor of inosine-5′-monophosphate dehydrogenase (IMPDH), an enzyme essential to the de novo synthesis of guanosine-5'-monophosphate (GMP) from inosine-5'-monophosphate (IMP).[32] IMPDH inhibition particularly affects lymphocytes since they rely almost exclusively on de novo purine synthesis.[33] In contrast, many other cell types use both pathways, and some cells, such as terminally differentiated neurons, depend completely on purine nucleotide salvage.[34] Thus, use of mycophenolic acid leads to a relatively selective inhibition of DNA replication in T cells and B cells.

Pharmacology

Mycophenolate can be derived from the fungi Penicillium stoloniferum, P. brevicompactum and P. echinulatum.[35] Mycophenolate mofetil is metabolised in the liver to the active moiety mycophenolic acid. It reversibly inhibits inosine monophosphate dehydrogenase,[36] the enzyme that 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.[37] Other cells recover purines via a separate salvage pathway and are thus able to escape the effect.[30]

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 is the morpholino ethyl ester of mycophenolic acid; the ester masks the carboxyl group.[40] Mycophenolate mofetil is reported to have a 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 Bartolomeo Gosio. Gosio collected a fungus from spoiled corn and named it Penicillium glaucum. (The species is now called P. brevicompactum.) In 1893 he found that the fungus had antibacterial activity. In 1896 he isolated crystals of the compound, which he successfully demonstrated as the active antibacterial compound against the anthrax bacterium.[18] This was the first antibiotic that was isolated in pure and crystalline form. But the discovery was forgotten.[41] It was rediscovered by two American scientists C.L. Alsberg and O.M. Black in 1912, and given the name mycophenolic acid. The compound was eventually demonstrated to have antiviral, antifungal, antibacterial, anticancer, and antipsoriasis activities.[42] Although it is not commercialised as antibiotic due to its adverse effects, its modified compound (ester derivative) is an approved immunosuppressant drug in kidney, heart, and liver transplantations, and is marketed under the brands CellCept (mycophenolate mofetil by Roche) and Myfortic (mycophenolate sodium by Novartis).[43]

Cellcept was developed by a South African geneticist Anthony Allison and his wife Elsie M. Eugui. In the 1970s while working at the Medical Research Council, Allison investigated the biochemical causes of immune deficiency in children. He discovered the metabolic pathway involving an enzyme, inosine monophosphate dehydrogenase, which is responsible for undesirable immune response in autoimmune diseases, as well as for immune rejection in organ transplantation. He conceived an idea that if a molecule that could block the enzyme is discovered, then, it would become an immunosuppressive drug that could be used for autoimmune diseases and in organ transplantation. In 1981 he decided to go for drug discovery and approached several pharmaceutical companies, which turned him down one by one as he had no primary knowledge of drug research. However, Syntex liked his plans and asked him to join the company with his wife.[44] He became vice president for the research. In one of their experiments the Allisons used an antibacterial compound, mycophenolate mofetil, which was abandoned in clinical use due to its adverse effects. They discovered that the compound had immunosuppressive activity.[45] [46] They synthesised a chemical variant for increased activity and reduced adverse effects.[47] [48] [49] [50] [51] They subsequently demonstrated that it was useful in organ transplantation in experimental rats.[52] [53] After successful clinical trials,[54] the compound was approved for use in kidney transplant by the 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.[58]

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.[59]

Research

Mycophenolate mofetil is beginning to be used in the management of auto-immune disorders such as idiopathic thrombocytopenic purpura (ITP), systemic lupus erythematosus (SLE), scleroderma (systemic sclerosis or SSc), and pemphigus vulgaris (PV) with success for some patients.[60]

It is also being used as a long-term therapy for maintaining remission of granulomatosis with polyangiitis, though thus far, studies have found it inferior to azathioprine. A combination of mycophenolate and ribavirin has been found to stop infection by and replication of dengue virus in vitro.[61] [62] It has also shown promising antiviral activity against MERS, especially in combination with interferon.[63]

Preliminary data suggest 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.[64]

Notes and References

  1. Web site: Mycophenolate mofetil (CellCept) Use During Pregnancy . Drugs.com . 24 January 2020 . 6 April 2020 . 28 October 2019 . https://web.archive.org/web/20191028143929/https://www.drugs.com/pregnancy/mycophenolate-mofetil.html . live .
  2. Web site: CellCept (mycophenolate mofetil) . Australian Product Information . 30 November 2021 . 8 January 2023 . 8 January 2023 . https://web.archive.org/web/20230108233340/https://www.guildlink.com.au/gc/ws/ro/pi.cfm?product=ropccept10215 . live .
  3. Web site: Pharmacor mycophenolate, mycocell, alcept (Pharmacor Pty Ltd) . Therapeutic Goods Administration (TGA) . 11 November 2022 . 29 April 2023 . 18 March 2023 . https://web.archive.org/web/20230318050718/https://www.tga.gov.au/resources/prescription-medicines-registrations/pharmacor-mycophenolate-mycocell-alcept-pharmacor-pty-ltd . live .
  4. Web site: CellCept 1g/5ml powder for oral suspension - Summary of Product Characteristics (SmPC) . (emc) . 27 February 2020 . 22 October 2020 . 25 September 2020 . https://web.archive.org/web/20200925163745/https://www.medicines.org.uk/emc/product/1569/smpc . live .
  5. Web site: Cellcept 250mg Capsules - Summary of Product Characteristics (SmPC) . (emc) . 17 June 2020 . 22 October 2020 . 25 September 2020 . https://web.archive.org/web/20200925173738/https://www.medicines.org.uk/emc/product/1102/smpc . live .
  6. Web site: Cellcept 500mg Film-Coated Tablets - Summary of Product Characteristics (SmPC) . (emc) . 22 October 2020 . 25 September 2020 . https://web.archive.org/web/20200925171640/https://www.medicines.org.uk/emc/product/1103/smpc . live .
  7. Web site: CellCept- mycophenolate mofetil tablet, film coated CellCept- mycophenolate mofetil capsule CellCept- mycophenolate mofetil hydrochloride injection, powder, lyophilized, for solution CellCept- mycophenolate mofetil powder, for suspension . DailyMed . 23 October 2020 . 24 October 2020 . https://web.archive.org/web/20201024084207/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=37241e87-4af4-4dc3-a1aa-ea6f20d8dc40 . live .
  8. Web site: Myhibbin- mycophenolate mofetil suspension . DailyMed . 7 May 2024 . 16 June 2024.
  9. Web site: CellCept. TGA eBusiness Services. Roche Products Pty Limited. 13 December 2012. 25 February 2014. PDF. 8 July 2020. https://web.archive.org/web/20200708204033/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-03448-3. live.
  10. Book: Schiff ER, Maddrey WC, Sorrell MF . Schiff's Diseases of the Liver . 2011 . John Wiley & Sons . 978-1-119-95048-6 . PT3219 . en . 23 September 2020 . 29 April 2023 . https://web.archive.org/web/20230429051159/https://books.google.com/books?id=HsxFSx_B4sUC&pg=PT3219 . live .
  11. Book: Laskin AI, Bennett JW, Gadd GM . Geoffrey Michael Gadd . Advances in Applied Microbiology . 2001 . Gulf Professional Publishing . 978-0-12-002648-7 . 236 . en . 23 September 2020 . 29 April 2023 . https://web.archive.org/web/20230429051159/https://books.google.com/books?id=0WqTtYOVPTMC&pg=PA236 . live .
  12. Web site: Mycophenolate Monograph for Professionals . Drugs.com . 28 October 2019 . en . 21 April 2020 . https://web.archive.org/web/20200421004944/https://www.drugs.com/monograph/mycophenolate.html . live .
  13. Book: British national formulary : BNF 76. 2018. Pharmaceutical Press. 978-0-85711-338-2. 826–827. 76.
  14. Web site: Mycophenolate Mofetil - Drug Usage Statistics . ClinCalc . 7 October 2022 . 8 July 2020 . https://web.archive.org/web/20200708162905/https://clincalc.com/DrugStats/Drugs/MycophenolateMofetil . live .
  15. Book: Rossi S . Australian Medicines Handbook . Australian Medicines Handbook . 2006 . Adelaide . Australian Medicines Handbook . 978-0-9757919-2-9 .
  16. Moore RA, Derry S . Systematic review and meta-analysis of randomised trials and cohort studies of mycophenolate mofetil in lupus nephritis . Arthritis Research & Therapy . 8 . 6 . R182 . 2006 . 17163990 . 1794528 . 10.1186/ar2093 . free .
  17. Book: Harber M. Practical nephrology. 2014. 978-1-4471-5547-8. 449. Harber M . Springer . 23 September 2020. 29 April 2023. https://web.archive.org/web/20230429051159/https://books.google.com/books?id=6GQgBAAAQBAJ&pg=PA449. live.
  18. Kitchin JE, Pomeranz MK, Pak G, Washenik K, Shupack JL . Rediscovering mycophenolic acid: a review of its mechanism, side effects, and potential uses . Journal of the American Academy of Dermatology . 37 . 3 Pt 1 . 445–9 . September 1997 . 9308561 . 10.1016/S0190-9622(97)70147-6 . free .
  19. D'Cruz DP, Khamashta MA, Hughes GR . Systemic lupus erythematosus . Lancet . 369 . 9561 . 587–96 . February 2007 . 17307106 . 10.1016/S0140-6736(07)60279-7 . 10.1.1.1008.5428 . 28468112 .
  20. Singh JA, Hossain A, Kotb A, Wells GA . Comparative effectiveness of immunosuppressive drugs and corticosteroids for lupus nephritis: a systematic review and network meta-analysis . Systematic Reviews . 5 . 1 . 155 . September 2016 . 27619512 . 5020478 . 10.1186/s13643-016-0328-z . free .
  21. Walsh M, James M, Jayne D, Tonelli M, Manns BJ, Hemmelgarn BR . Mycophenolate mofetil for induction therapy of lupus nephritis: a systematic review and meta-analysis . Clinical Journal of the American Society of Nephrology . 2 . 5 . 968–75 . September 2007 . 17702723 . 10.2215/CJN.01200307 . free .
  22. Knight SR, Russell NK, Barcena L, Morris PJ . Mycophenolate mofetil decreases acute rejection and may improve graft survival in renal transplant recipients when compared with azathioprine: a systematic review . Transplantation . 87 . 6 . 785–94 . March 2009 . 19300178 . 10.1097/TP.0b013e3181952623 . 33596652 . free .
  23. Remuzzi G, Lesti M, Gotti E, Ganeva M, Dimitrov BD, Ene-Iordache B, Gherardi G, Donati D, Salvadori M, Sandrini S, Valente U, Segoloni G, Mourad G, Federico S, Rigotti P, Sparacino V, Bosmans JL, Perico N, Ruggenenti P . Mycophenolate mofetil versus azathioprine for prevention of acute rejection in renal transplantation (MYSS): a randomised trial . Lancet . 364 . 9433 . 503–12 . 2004 . 15302193 . 10.1016/S0140-6736(04)16808-6 . 22033113 .
  24. Web site: CellCept, Myfortic (mycophenolate) dosing, indications, interactions, adverse effects, and more. reference.medscape.com. 9 November 2014. 30 April 2021. https://web.archive.org/web/20210430035139/https://reference.medscape.com/drug/cellcept-myfortic-mycophenolate-343209#4. live.
  25. Web site: Homepage - BNF Publications . www.bnf.org. 9 November 2014. 27 April 2021. https://web.archive.org/web/20210427213820/https://www.bnf.org/. live.
  26. Web site: CellCept (mycophenolate mofetil) August 2009 . 14 August 2009 . 21 August 2009 . . 21 August 2009 . https://web.archive.org/web/20090821063629/http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm177397.htm . live .
  27. Web site: CellCept (mycophenolate mofetil) August 2009 . 14 August 2009 . 21 August 2009 . . 21 August 2009 . https://web.archive.org/web/20090821063629/http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm177397.htm . live .
  28. Web site: FDA Issues Second CellCept Warning . newsinferno.com . 18 May 2008 . 26 October 2010 . 24 February 2013 . https://web.archive.org/web/20130224081912/http://www.newsinferno.com/archive/fda-issues-second-cellcept-warning/ . dead .
  29. Web site: MedWatch Safety Alerts for Human Medical Products . fda.gov . May 2008 . 26 October 2010 . 19 October 2010 . https://web.archive.org/web/20101019142831/http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm092157.htm . live .
  30. Book: Austria-Codex. Jasek W . Österreichischer Apothekerverlag. Vienna. 2007. 62nd. 1484–95. 978-3-85200-181-4. de.
  31. Drugs.com: Mycophenolic acid
  32. Book: Pharmacology North American Edition.. 2014. Lippincott Williams & Wilkins. 978-1-4511-9177-6. 625.
  33. Book: Parnham FP, Nijkamp MJ . Principles of immunopharmacology. limited . 2005. Birkhèauser Verlag. Basel. 978-3764358044. 453. 2nd rev. and extended.
  34. Fu R, Ceballos-Picot I, Torres RJ, Larovere LE, Yamada Y, Nguyen KV, Hegde M, Visser JE, Schretlen DJ, Nyhan WL, Puig JG, O'Neill PJ, Jinnah HA . Genotype-phenotype correlations in neurogenetics: Lesch-Nyhan disease as a model disorder . Brain . 137 . Pt 5 . 1282–303 . May 2014 . 23975452 . 3999711 . 10.1093/brain/awt202 .
  35. Anderson HA, Bracewell JM, Fraser AR, Jones D, Robertson GW, Russell JD . 5-Hydroxymaltol and mycophenolic acid, secondary metabolites from Penicillium echinulatum. Transactions of the British Mycological Society. December 1988. 91. 4. 649–651. 10.1016/S0007-1536(88)80040-8.
  36. Fulton B, Markham A . Mycophenolate mofetil. A review of its pharmacodynamic and pharmacokinetic properties and clinical efficacy in renal transplantation . Drugs . 51 . 2 . 278–98 . February 1996 . 8808168 . 10.2165/00003495-199651020-00007 . 46954073 .
  37. Ransom JT . Mechanism of action of mycophenolate mofetil . Therapeutic Drug Monitoring . 17 . 6 . 681–4 . December 1995 . 8588241 . 10.1097/00007691-199512000-00023 . 6439393 .
  38. Dooley MA, Jayne D, Ginzler EM, Isenberg D, Olsen NJ, Wofsy D, Eitner F, Appel GB, Contreras G, Lisk L, Solomons N . Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis . The New England Journal of Medicine . 365 . 20 . 1886–95 . November 2011 . 22087680 . 10.1056/NEJMoa1014460 . 27689350 . free . 25 November 2021 . 8 March 2022 . https://web.archive.org/web/20220308023022/https://cdr.lib.unc.edu/downloads/8623j6697 . live . 20.500.12648/8250 . free .
  39. Zhang W, Ding C, Zheng S . Enteric-coated mycophenolate sodium: an update . International Journal of Clinical Practice. Supplement . 68. 181 . 1–3 . April 2014 . 24673712 . 10.1111/ijcp.12399 . 2630344 . free .
  40. Lipsky JJ . Mycophenolate mofetil . Lancet . 348 . 9038 . 1357–9 . November 1996 . 8918281 . 10.1016/S0140-6736(96)10310-X . 36837474 .
  41. Book: Zhang L, Demain AL . Natural Products: Drug Discovery and Therapeutic Medicine. 2005. Humana Press. Totowa, N.J.. 978-1-59259-976-9. 14. 16 August 2019. 29 April 2023. https://web.archive.org/web/20230429051222/https://books.google.com/books?id=iP0i7x_38ZwC. live.
  42. Regueira TB, Kildegaard KR, Hansen BG, Mortensen UH, Hertweck C, Nielsen J . Molecular basis for mycophenolic acid biosynthesis in Penicillium brevicompactum . Applied and Environmental Microbiology . 77 . 9 . 3035–43 . May 2011 . 21398490 . 3126426 . 10.1128/AEM.03015-10 . 2011ApEnM..77.3035R .
  43. Bentley R . Mycophenolic Acid: a one hundred year odyssey from antibiotic to immunosuppressant . Chemical Reviews . 100 . 10 . 3801–26 . October 2000 . 11749328 . 10.1021/cr990097b .
  44. Watts G . Anthony Clifford Allison. The Lancet. 2014. 383. 9925. 1290. 10.1016/S0140-6736(14)60635-8. 54281245 . free.
  45. Allison AC . Immunosuppressive drugs: the first 50 years and a glance forward . Immunopharmacology . 47 . 2–3 . 63–83 . May 2000 . 10878284 . 10.1016/S0162-3109(00)00186-7 .
  46. Allison AC, Kowalski WJ, Muller CD, Eugui EM . Mechanisms of action of mycophenolic acid . Annals of the New York Academy of Sciences . 696 . 1 . 63–87 . November 1993 . 7906496 . 10.1111/j.1749-6632.1993.tb17143.x . 1993NYASA.696...63A . 34520788 .
  47. Nelson PH, Eugui E, Wang CC, Allison AC . Synthesis and immunosuppressive activity of some side-chain variants of mycophenolic acid . Journal of Medicinal Chemistry . 33 . 2 . 833–8 . February 1990 . 1967654 . 10.1021/jm00164a057 .
  48. Eugui EM, Allison AC . Immunosuppressive activity of mycophenolate mofetil . Annals of the New York Academy of Sciences . 685 . 1 . 309–29 . June 1993 . 8363235 . 10.1111/j.1749-6632.1993.tb35881.x . 1993NYASA.685..309E . 9028169 .
  49. Allison AC, Eugui EM . Purine metabolism and immunosuppressive effects of mycophenolate mofetil (MMF) . Clinical Transplantation . 10 . 1 Pt 2 . 77–84 . February 1996 . 8680053 .
  50. Allison AC, Eugui EM . The design and development of an immunosuppressive drug, mycophenolate mofetil . Springer Seminars in Immunopathology . 14 . 4 . 353–80 . 1993 . 8322167 . 10.1007/bf00192309 . 26433174 .
  51. Allison AC, Eugui EM . Immunosuppressive and other effects of mycophenolic acid and an ester prodrug, mycophenolate mofetil . Immunological Reviews . 136 . 1 . 5–28 . December 1993 . 7907572 . 10.1111/j.1600-065x.1993.tb00652.x . 711727 .
  52. Bechstein WO, Suzuki Y, Kawamura T, Jaffee B, Allison A, Hullett DA, Sollinger HW . Low-dose combination therapy of DUP-785 and RS-61443 prolongs cardiac allograft survival in rats . Transplant International . 5 . Suppl 1 . S482-3 . 1992 . 14621853 . 10.1111/tri.1992.5.s1.482 . 222199749 .
  53. Kawamura T, Hullett DA, Suzuki Y, Bechstein WO, Allison AM, Sollinger HW . Enhancement of allograft survival by combination RS-61443 and DUP-785 therapy . Transplantation . 55 . 4 . 691–4; discussion 694–5 . April 1993 . 8475537 . 10.1097/00007890-199304000-00001 . free .
  54. Taylor DO, Ensley RD, Olsen SL, Dunn D, Renlund DG . Mycophenolate mofetil (RS-61443): preclinical, clinical, and three-year experience in heart transplantation . The Journal of Heart and Lung Transplantation . 13 . 4 . 571–82 . 1994 . 7947873 .
  55. Web site: Risk Evaluation and Mitigation Strategy (REMS) Under Review for CellCept and Myfortic. U.S. Food and Drug Administration. 23 July 2014. 8 August 2014. https://web.archive.org/web/20140808102218/http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm148735.htm. live.
  56. Web site: Donlon DM . New Agent to Prevent Kidney Transplant Rejection Now Available. Stanford University. 23 July 2014. 15 June 1995. 27 July 2014. https://web.archive.org/web/20140727040934/http://web.stanford.edu/dept/HPS/transplant/html/cell-cept.htm. live.
  57. Web site: CellCept registry data demonstrated superior long-term organ transplant outcomes. Roche.com. F. Hoffmann-La Roche Ltd.. 23 July 2014. dead. https://web.archive.org/web/20140726060253/http://www.roche.com/investors/ir_update/inv-update-2004-05-17a.htm. 26 July 2014.
  58. Web site: CellCept EPAR . European Medicines Agency (EMA) . 17 September 2018 . 6 April 2020 . 6 April 2020 . https://web.archive.org/web/20200406184051/https://www.ema.europa.eu/en/medicines/human/EPAR/cellcept . live .
  59. van Gelder T, Hesselink DA . Mycophenolate revisited . Transplant International . 28 . 5 . 508–15 . May 2015 . 25758949 . 10.1111/tri.12554 . 1673466 . free .
  60. Mimouni D, Anhalt GJ, Cummins DL, Kouba DJ, Thorne JE, Nousari HC . Treatment of pemphigus vulgaris and pemphigus foliaceus with mycophenolate mofetil . Archives of Dermatology . 139 . 6 . 739–42 . June 2003 . 12810504 . 10.1001/archderm.139.6.739 . free .
  61. Diamond MS, Zachariah M, Harris E . Mycophenolic acid inhibits dengue virus infection by preventing replication of viral RNA . Virology . 304 . 2 . 211–21 . December 2002 . 12504563 . 10.1006/viro.2002.1685 . free .
  62. Takhampunya R, Ubol S, Houng HS, Cameron CE, Padmanabhan R . Inhibition of dengue virus replication by mycophenolic acid and ribavirin . The Journal of General Virology . 87 . Pt 7 . 1947–52 . July 2006 . 16760396 . 10.1099/vir.0.81655-0 . free .
  63. Chan JF, Chan KH, Kao RY, To KK, Zheng BJ, Li CP, Li PT, Dai J, Mok FK, Chen H, Hayden FG, Yuen KY . Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus . The Journal of Infection . 67 . 6 . 606–16 . December 2013 . 24096239 . 10.1016/j.jinf.2013.09.029 . 7112612 . free .
  64. Xiao Y, Huang J, Luo H, Wang J . Mycophenolate mofetil for relapsing-remitting multiple sclerosis . The Cochrane Database of Systematic Reviews . 2 . CD010242 . February 2014 . 2014 . 24505016 . 10.1002/14651858.CD010242.pub2 . free . 10875409 .

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Mycophenolic acid".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.