Mycophenolate

Mycophenolic acid, (MPA) is a non-competitive reversible inhibitor of the inosine monophosphate dehydrogenase (IMPDH), a key rate-limiting enzyme in the de novo purine synthesis pathway and also called mycophenolate, is an immunosuppressant drug used to prevent rejection in organ transplantation. It was initially introduced as the prodrug mycophenolate mofetil (MMF, trade name CellCept) to improve oral bioavailability. More recently, the salt mycophenolate sodium (trade name Myfortic) has also been introduced. Enteric-coated mycophenolate sodium is an alternative MPA formulation. However, the kinetics of EC-MPS differ in that the drug is enteric coated, dissolves at pH levels of ≥ 5,with the goal of delaying the delivery of MPA until it reaches the small intestine Mycophenolic acid, (MPA) is a non-competitive reversible inhibitor of the inosine monophosphate dehydrogenase (IMPDH), a key rate-limiting enzyme in the de novo purine synthesis pathway and also called mycophenolate, is an immunosuppressant drug used to prevent rejection in organ transplantation. It was initially introduced as the prodrug mycophenolate mofetil (MMF, trade name CellCept) to improve oral bioavailability. More recently, the salt mycophenolate sodium (trade name Myfortic) has also been introduced. Enteric-coated mycophenolate sodium is an alternative MPA formulation. However, the kinetics of EC-MPS differ in that the drug is enteric coated, dissolves at pH levels of ≥ 5,with the goal of delaying the delivery of MPA until it reaches the small intestine Discovered by Italian medical scientist Bartolomeo Gosio in 1893, mycophenolic acid was the first antibiotic to be synthesised in pure and crystalline form. But its medical application was forgotten until two American scientists C.L. Alsberg and O.M. Black resynthesised it in 1912, and gave its chemical name. It was eventually found to be a broad-spectrum acting drug having antiviral, antifungal, antibacterial, anticancer, and antipsoriasis properties. The clinically usable drug Cellcept was developed by South African geneticist Anthony Allison and his wife Elsie M. Eugui. It was first approved in the United States in 1995 for use in kidney transplantation. Mycophenolate is used for the prevention of organ transplant rejection. Mycophenolate mofetil is indicated for the prevention of organ transplant rejection in adults and renal transplant rejection in children over 2 years; whereas 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, or lung transplants in children older than two years. It is also used for retroperitoneal fibrosis along with a number of other medications. An immunosuppressant that has decreased the incidence of acute rejection in solid transplant recipients, mycophenolate is increasingly utilized as a steroid sparing treatment in autoimmune diseases and similar immune-mediated disorders including Behçet's disease, pemphigus vulgaris, refractory incomplete systemic lupus erythematosus, immunoglobulin A nephropathy, small vessel vasculitides, and psoriasis. Its increasing application in treating lupus nephritis has demonstrated more frequent complete response and less frequent complications compared to cyclophosphamide bolus therapy, a regimen with risk of bone marrow suppression, infertility, and malignancy. Further work addressing maintenance therapy demonstrated mycophenolate superior to cyclophosphamide, again in terms of response and side-effects. Walsh proposed that mycophenolate should be considered as a first-line induction therapy for treatment of lupus nephritis in people without kidney dysfunction. Compared with azathioprine it has higher incidence of diarrhea, and no difference in risk of any of the other side effects. Mycophenolic acid is 15 times more expensive than azathioprine. The exact role of mycophenolate vs azathioprine has yet to be conclusively established. Common adverse drug reactions (≥1% of patients) associated with mycophenolate therapy include diarrhea, nausea, vomiting, joint pain; infections, leukopenia, and/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 patients) include esophagitis, gastritis, gastrointestinal tract hemorrhage, and/or invasive cytomegalovirus (CMV) infection. 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.Several cases of pure red cell aplasia (PRCA) have also been reported. The U.S. Food and Drug Administration (FDA) has issued an alert that patients on mycophenolate mofetil and mycophenolic acid 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 patients 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. Mycophenolic acid is associated with miscarriage and congenital malformations when used during pregnancy, and should be avoided whenever possible by women trying to conceive.