Mofetil CellCept

Mycophenolic acid (MPA) was isolated from cultures of Penicillium spp. in 1896 and was purified in 1913. Initially the compound was studied for its antifungal and antibacterial effects and later for its antitumor effects. Many years later, its immunosuppressive activities were recognized and after further developmental work, an ester prodrug mycophenolate mofetil was developed, which was approved by the United States Food and Drug Administration for the prevention of acute renal allograft rejection in 1995 and for heart transplant recipients in 1998. Mycophenolate mofetil is a cytotoxic agent now used for immunosuppressive therapy and is the mofetil ester of MPA, which is the active immunosuppressive agent. 

Mycophenolate mofetil is a functionally selective cytotoxic agent for B and T lymphocytes, where it blocks the production of guanosine nucleotides required for DNA synthesis. For purine biosynthesis, B and T lymphocytes rely on de novo synthesis rather than on the salvage pathway. Lymphocytes have little or no salvage pathway as opposed to other blood marrow elements and parenchymal cells that 

Mycophenolate mofetil is rapidly absorbed after oral administration, and the bioavailability of its oral dose is 94%. It is metabolized by esterases to free MPA, which is the active metabolite. The enterohepatic recirculation plays a crucial role in the serum levels of MPA. The active metabolite is further metabolized by glucuronyl transferase and is eliminated (90%) in urine as the MPA glucuronide (MPAG) as a result of the organic anion transport system in the proximal tubule. A small amount is excreted in feces. 

The coadministration of mycophenolate mofetil with antacids results in decreased absorption. The plasma MPA concentration is significantly reduced by cholestyramine due to binding of the cholestyramine to MPAG in the intestine and interfering with the enterohepatic recirculation of the drug. The bioavailability of mycophenolate mofetil is higher when administered with tacrolimus as opposed to cyclosporine. The bioavailability of MPA is reduced by antibiotics including fluoroquinolones and metronidazole. 

The side effects of mycophenolate mofetil include diarrhea, abdominal pain, constipation, nausea/vomiting, acne, dyspnea, cough, peripheral edema, increased risk of infections, drug-induced fever, dizziness, headaches, leukopenia and anemia. 

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Mycophenolate mofetil (CellCept) inhibits DNA and RNA synthesis and has been shown to have a specific lymphocyte antiproliferative effect. Although not FDA approved for this indication, oral mycophenolate mofetil appears effective in the treatment of moderate to severe plaque psoriasis. The usual dose is 500 mg orally four times a day, up to a maximum of 4 g/day. Common adverse effects include GI toxicity (diarrhea, nausea, vomiting), hematologic effects (anemia, neutropenia, thrombocytopenia), and viral and bacterial infections. Lymphoproliferative disease or lymphoma has been reported. 

Parenteral 5 mg/5 mL ampule for injection Mycophenolate mofetil (CellCept, Myfortic)... 

Clinical Use. Mycophenolate mofetil (CellCept) is primarily used to prevent or treat organ rejection following cardiac and renal transplantation. This drug is typically combined with other immunosuppressants (cyclosporine, glucocorticoids) to provide optimal immunosuppression in patients receiving these transplant types.39,40,70 Mycophenolate mofetil may also be useful in suppressing the immune response associated with autoimmune conditions such as systemic lupus erythematosus.2... 

SLE appears to be steroid responsive only in the early coiu se of the disease. Optic atrophy occiu s in untreated cases, with the development of permanent visual field defects. Therapy includes high-dose intravenous methyl-prednisolone, oral prednisone, or steroid-sparing medications such as mycophenolate mofetil (CellCept). A rheumatology referral is also advised. 

Antimetabolites selectively compete for intermediary metabolites critical to immime cell function, exerting a cytotoxic effect. Methotrexate (Folex ), which inhibits folic acid, is the most widely recognized and used drug in this class. Other antimetabolites that may be used in treating uveitis include azathioprine (Imuran ) and mycophe-nolate mofetil (CellCept ), both of which interfere with purine metabolism. 

Behrend M. Mycophenolate mofetil Cellcept. Expert Opin. In-... 

Mycophenolate mofetil (Cellcept) is the 2-morpholino-ethyl ester of mycophenolic acid (MPA). 

Mycophenolate mofetil (Cellcept) is an immunosuppressant approved for prophylaxis of organ rejection in patients with renal, cardiac, and hepatic transplants. Myco-phenolic acid, the active derivative of mycophenolate mofetil, inhibits the enzyme inosine monophosphatase dehydrogenase (IMPDH), thereby depleting guanosine nucleotides essential for DNA and RNA synthesis. Moreover, mycophenolic acid is a fivefold more potent inhibitor of the type 11 isoform of IMPDH found in activated B- and T-lymphocytes and thus functions as a specific inhibitor of T- and B-lymphocyte activation and proliferation. The drug also may enhance apoptosis. 

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