Immunosuppressive agents mycophenolate mofetil

Selective immunosuppressive agents mycophenolate mofetil sirolimus tacrolimus... 

Keywords Acetylcholine Autonomic nervous system Cyclosporine Epinephrine General anesthetics Immunostimu-lating agents Immunosuppressive agents Mycophenolate mofetil Opioid drugs Sedative-hypnotic agents... 

Neyts J, Andrei G, De Clercq E. The novel immunosuppressive agent mycophenolate mofetil markedly potentiates the antiherpesvirus activities of acyclovir, ganciclovir, and penciclovir in vitro and in vivo. Antimicrob Agents Chemother 1998 42(2) 216-22. 

Mycophenolate mofetil Esterification of the immunosuppressive agent mycophenolic add (MMA) leads to mycophenolate mofetil (MME) as a prodrug with improved oral bioavailability. MMF (2 g/day) was first administered in PBC, combined with UDCA, by E.A. Jones et al. in 1999. In a later study, they were able to confirm thdr good results (based on selectively and reversibly inhibiting... 

Mycophenolic acid (MPA) was first isolated from the Penicillin glaucum mold. It was first smdied as an antibiotic but later was found to have immunosuppressive properties. Mycophenolate mofetil (MMF) the morpholinoethyl ester of MPA appears to be a specific immunosuppressant for lymphocytes, resulting in fewer adverse effects than azathioprine, making it the preferred agent over azathioprine. 

FK-506 (37) interferes with IL-2 synthesis and release and has a cyclosporin-like profile, but is considerably more potent in vitro. IC q values are approximately 100-fold lower. This neutral macroHde suppresses the mixed lymphocyte reaction T-ceU proliferation generation of cytotoxic T-ceUs production of T-ceU derived soluble mediators, such as IL-2, IL-3, and y-IFN and IL-2 receptor expression (83). StmcturaHy, FK-506 is similar to sirolimus. Mycophenolate mofetil (33), brequinar (34), and deoxyspergualin are in various phases of clinical evaluation. Identification of therapeutic efficacy and safety are important factors in the deterrnination of their utiUty as immunosuppressive agents. 

Mycophenolate mofetil was approved by the FDA in 1995, and enteric-coated mycophenolic acid was approved in 2004. Both agents are considered to be adjunctive immunosuppressants. Mycophenolic acid acts by inhibiting inosine monophosphate deydrogenase, a vital enzyme in the de novo pathway of purine synthesis. Inhibition of this enzyme prevents the proliferation of most cells that are dependent on the de novo pathway for purine synthesis, including T cells.7,11,26-28... 

MPA derivatives have replaced azathioprine as the antiproliferative agent of choice in most organ transplant centers. The MPA derivatives generally are considered to provide a more specific immunosuppressive effect compared with azathioprine. Mycophenolate mofetil and enteric-coated mycophe-nolic acid have similar safety and efficacy data in renal transplant recipients. 

Sirolimus is currently the only FDA-approved ToR inhibitor. One of its derivatives, everolimus, is in phase III clinical trials and has been approved for use in some European countries.30 Sirolimus is a macrolide antibiotic that has no effect on cal-cineurin phosphatase.11,31,32 Sirolimus inhibits T cell activation and proliferation by binding to and inhibiting the activation of the mammalian ToR, which suppresses cellular response to IL-2 and other cytokines (i.e., IL-4 and IL-15J.11,31 Studies have shown that sirolimus may be used safely and effectively with either cyclosporine or tacrolimus as a replacement for either azathioprine or mycophenolate mofetil.33 However, when using both sirolimus and cyclosporine as part of a patient s immunosuppressant therapy, because of a drug interaction between the two resulting in a marked increase in sirolimus concentrations, it is recommended to separate the sirolimus and cyclosporine doses by at least 4 hours. Sirolimus also can be used as an alternative agent for patients who do not tolerate calcineurin inhibitors due to nephrotoxicity or other adverse events.34... 

Cytotoxic agents which are exclusively used to achieve immunosuppression are azathioprine and mycophenolate mofetil, although their over all mechanism of action is similar to that of the antitumor dmgs, i.e. inhibition of lymphocyte proliferation after antigen exposure. 

Mycophenolate mofetil (MMF, CellCept) is an ester prodrug of mycophenolic acid (MPA), a Penicillium-de-rived immunosuppressive agent (see Chapter 57) that blocks de novo purine synthesis by noncompetitively inhibiting the enzyme inosine monophosphate dehydrogenase. MPA preferentially suppresses the proliferation of cells, such as T and B lymphocytes, that lack the purine salvage pathway and must synthesize de novo... 

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. 

Daclizumab is used for the prophylaxis of acute rejection in patients receiving kidney transplants. A dose of 1 mg/kg is sufficient to completely block all the IL-2 receptors. It is administered in five doses at a 2-week interval where its elimination half-life is about 20 days. A combination of several other immunosuppressive agents including cyclosporine (or tacrolimus, rapamycin), mycophenolate mofetil and corticosteroids can be used with daclizumab. When it is used in combination with tacrolimus, the doses of tacrolimus are reduced. After tissue transplantation, the addition of daclizumab to the standard immunosuppressive regimen produces reduction in tissue rejection up to 50%. Daclizumab can cause hypersensitivity reactions, but it does not cause cytokine-release syndrome. There is a low incidence of... 

Immunosuppressive drugs can be divided into five basic categories. Corticosteroids such as methylprednisolone and prednisone are a part of virtually all immunosuppressive drug regimens. Corticosteroids block the production of IL-1 and have potent anti-inflammatory effects. Calcineurin inhibitors such as cyclosporine and tacrolimus are also used in a majority of immunosuppressive drug regimens. Calcineurin inhibitors inhibit the production and secretion of IL-2. IL-2 is involved with T-lymphocyte activation and proliferation. Antiproliferative agents such as azathioprine, mycophenolate mofetil, and sirolimus block T-lymphocyte... 

Mycil chlorphenesin tolnafitate. mycophenolate mofetil [usan] (CellCept ) is converted in vivo to n cophenolic add, which has antimetabolite cytotoxic properties. It shows experimental activity as an ANTICANCER and ANTIVIRAL AGENT. It may be clinically useful in treating psoriasis and as an ANTU.EISHMANIAL. It shows IMMUNOSUPPRESSANT properties, and is used in the prophylaxis of acute kidney rejection, mycophenolic acid [ban, inn, usan] is usually... 

Commonly reported adverse effects of mycophenolate mofetil include gastrointestinal toxicity (diarrhea, nausea, and vomiting), hematologic effects (anemia, neutropenia, and thrombocytopenia), and an increased incidence of viral and bacterial infections. Lym-phoproliferative disease or lymphoma has developed in up to 1 % of patients who received mycophenolic acid with other immunosuppressive agents. 

Mycophenolate mofetil (MMF), an immunosuppressant used in organ transplant, has cleared refractory symptoms of AD in short-term, open-label studies. Since dose finding and weU-controlled studies are not available for MMF use in AD, the agent should be used with caution and discontinued if the patient does not respond within 4 to 8 weeks of therapy. ... 

The advent of potent non-nephrotoxic immunosuppressive agents might make the replacement of CsA or the decrease to it exposure in drugs protocols more feasible. At the moment, mofetil mycophenolate and sirolimus are the only commercially available new... 

Choudhary A, Harding SP, Bucknall RC, et al. Mycophenolate mofetil as an immunosuppressive agent in refractory inflammatory eye disease. J Ocul Pharmacol Ther 2006 22(3) 168-175. 

When detected by biopsy, rejection is treated aggressively by increasing the level of immunosuppression and the dose of corticosteroids (Winkel et al. 1999). In severe cases, additional agents such as antithymocyte globulin, OKT3, cyclophosphamide, methotrexate, vincristine, tacrolimus, rapamycin, or mycophenolate mofetil maybe required (Knisely... 

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