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Lupus 2005Mycophenolate mofetil (MMF) is an immunosuppressive agent used in transplantation, with evidence of superior protection against acute transplant rejection compared to... (Review)
Review
Mycophenolate mofetil (MMF) is an immunosuppressive agent used in transplantation, with evidence of superior protection against acute transplant rejection compared to azathioprine-containing regimens. Subsequently MMF has been used in a variety of autoimmune conditions. The major experience in systemic lupus erythematosus (SLE) has focused on proliferative lupus nephritis. Following its success in the treatment of lupus nephritis, MMF is now being used to control other SLE manifestations such as, lupus disease activity, haematological manifestations and resistant skin lupus. In this review, we discuss our own experience and the literature report about the use of MMF in SLE.
Topics: Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Mycophenolic Acid
PubMed: 15803925
DOI: 10.1191/0961203305lu2111oa -
Therapeutic Drug Monitoring Dec 1995
Review
Topics: Animals; Drug Monitoring; Enzyme Inhibitors; Humans; IMP Dehydrogenase; Immunosuppressive Agents; Mycophenolic Acid
PubMed: 8588243
DOI: 10.1097/00007691-199512000-00025 -
Current Opinion in Nephrology and... Sep 1999The immunosuppressive drug mycophenolate mofetil is a potential new treatment for autoimmune renal disease. In addition to its effects in modulating the autoimmune... (Review)
Review
The immunosuppressive drug mycophenolate mofetil is a potential new treatment for autoimmune renal disease. In addition to its effects in modulating the autoimmune response, mycophenolate mofetil reduces adhesion molecule expression and delays the progression of renal failure. Data from experimental models of glomerulonephritis, especially of lupus nephritis, have demonstrated that mycophenolate mofetil reverses both inflammatory and autoimmune aspects of disease and influences outcome. As yet, clinical experience with mycophenolate mofetil remains anecdotal but provides a strong platform for the scientific evaluation of mycophenolate mofetil as a new therapeutic agent for these conditions in the future.
Topics: Animals; Autoimmune Diseases; Disease Models, Animal; Glomerulonephritis; Humans; Immunosuppressive Agents; Kidney Diseases; Lupus Nephritis; Mycophenolic Acid; Vasculitis
PubMed: 10541218
DOI: 10.1097/00041552-199909000-00005 -
Journal of the American Academy of... Dec 2005
Topics: Humans; Immunosuppressive Agents; Mycophenolic Acid; Skin Diseases
PubMed: 16310066
DOI: 10.1016/j.jaad.2005.08.034 -
Drugs Feb 1996Mycophenolate mofetil is an ester prodrug of the active immunosuppressant mycophenolic acid. It is a noncompetitive, selective and reversible inhibitor of inosine... (Review)
Review
Mycophenolate mofetil is an ester prodrug of the active immunosuppressant mycophenolic acid. It is a noncompetitive, selective and reversible inhibitor of inosine monophosphate dehydrogenase, an important enzyme in the de novo synthesis of guanosine nucleotides in T and B lymphocytes. Mycophenolate mofetil and/or mycophenolic acid inhibit the proliferation of lymphocytes and the production of antibodies induced by a variety of mitogens and antigens. Mycophenolate mofetil is also active in several animal models of transplantation and has produced effects in animals that indicate that it may inhibit the chronic rejection process. Mycophenolate mofetil has been compared with azathioprine or placebo in 3 large, randomised, double-blind, multicentre trials as part of combination immunosuppression therapy with cyclosporin and corticosteroids. Compared with either placebo or azathioprine (1 to 2 mg/kg/day or 100 to 150 mg/day), mycophenolate mofetil 2 or 3 g/day was associated with a significantly lower proportion of patients experiencing acute rejection or treatment failure during the first 6 months after transplantation. Mycophenolate mofetil also tended to be associated with a lower proportion of patients who required a full course of antirejection therapy. However, the proportion of patients who died or who had graft loss was similar between all of the treatment groups. There are currently no data regarding the effects of mycophenolate mofetil on long term patient or graft survival, which are important clinical outcomes in assessing its place in the management of renal transplantation. Clinical trials are also needed to evaluate mycophenolate mofetil in specific patient populations (e.g. repeat renal transplant patients or highly sensitised patients), to determine its efficacy in alternative immunosuppressive protocols and to investigate its use in the transplantation of other solid organs. In summary, mycophenolate mofetil appears to be an attractive new agent in the prevention of graft rejection in renal transplant recipients that has shown superior efficacy to azathioprine. Although long term clinical outcome data are required, mycophenolate is a potentially important advance in transplant immunosuppression.
Topics: Animals; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid
PubMed: 8808168
DOI: 10.2165/00003495-199651020-00007 -
Expert Opinion on Pharmacotherapy Nov 2003Mycophenolate mofetil is an important drug in the modern immunosuppressive arsenal. Mycophenolate mofetil is the semisynthetic morpholinoethyl ester of mycophenolate... (Review)
Review
Mycophenolate mofetil is an important drug in the modern immunosuppressive arsenal. Mycophenolate mofetil is the semisynthetic morpholinoethyl ester of mycophenolate acid. Mycophenolate acid prevents T and B cell proliferation by specifically inhibiting a purine pathway required for lymphocyte division. This paper extensively reviews the experience of mycophenolate mofetil use in liver transplant recipients. In randomised trials, mycophenolate mofetil decreased the rate of acute rejection after liver transplantation, without a significant increase of septic complications. However, so far, there are no data indicating that mycophenolate mofetil increases liver transplant patient or graft survivals. Mycophenolate mofetil is interesting because of its particular side effects profile, which is very different from the other immunosuppressants. The absence of mycophenolate mofetil nephrotoxicity is of specific interest in liver recipients with impairment of renal function. The monitoring of mycophenolate acid area under the concentration time curve might be interesting to limit side effects and provide better clinical efficacy but the exact role of mycophenolate acid monitoring in liver recipients has yet to be further evaluated in large series.
Topics: Animals; Graft vs Host Disease; Humans; Immunosuppressive Agents; Liver Transplantation; Mycophenolic Acid
PubMed: 14596648
DOI: 10.1517/14656566.4.11.1949 -
Annals of the New York Academy of... Sep 2007The immunosuppressive agent mycophenolate mofetil (MMF) has beneficial effects in cardiac transplant patients beyond the suppression of tissue rejection. Patients with... (Review)
Review
The immunosuppressive agent mycophenolate mofetil (MMF) has beneficial effects in cardiac transplant patients beyond the suppression of tissue rejection. Patients with regimens containing MMF experience diminished intimal thickening and cardiac allograft vasculopathy compared to patients treated with azathioprine. Studies have shown that diet-induced atherosclerosis (a related vasculopathy) is a chronic inflammatory process, and so MMF has also been used to reduce atherosclerosis in a rabbit model of hyperlipidemia. These data hold out the intriguing possibility that MMF might be a viable primary or secondary preventive agent in people at significant risk for atherosclerosis.
Topics: Animals; Atherosclerosis; Disease Models, Animal; Humans; Mycophenolic Acid
PubMed: 17911436
DOI: 10.1196/annals.1423.023 -
Der Hautarzt; Zeitschrift Fur... Feb 2000Mycophenolate mofetil represents a new immunosuppressive drug. Several case reports have shown that mycophenolate mofetil has a good therapeutic effect in patients with... (Review)
Review
Mycophenolate mofetil represents a new immunosuppressive drug. Several case reports have shown that mycophenolate mofetil has a good therapeutic effect in patients with psoriasis and autoimmune dermatoses. Mycophenolate mofetil is a morpholine ester of mycophenolic acid which was shown in the 1970s to be effective in patients with severe psoriasis. Mycophenolate mofetil has an increased bioavailability as compared to mycophenolic acid and thereby an improved therapeutic window. Currently, mycophenolate mofetil is indicated for the prevention of organ rejection in transplant patients. The mode of action and the pharmacology of mycophenolate mofetil are reviewed and the current clinical experience with this immunosuppressive drug for dermatological disorders is summarized.
Topics: Administration, Oral; Animals; Autoantibodies; Autoimmune Diseases; Clinical Trials as Topic; Humans; Immunosuppressive Agents; Mycophenolic Acid; Psoriasis; Skin Diseases; Treatment Outcome
PubMed: 10743574
DOI: 10.1007/s001050050013 -
Drugs 2005Mycophenolate mofetil is one of the most frequently used immunosuppressive drugs in solid organ transplantation. Although the adverse effect profile of mycophenolate... (Comparative Study)
Comparative Study Review
Mycophenolate mofetil is one of the most frequently used immunosuppressive drugs in solid organ transplantation. Although the adverse effect profile of mycophenolate mofetil is comparatively benign, gastrointestinal adverse effects are a major concern. The adverse effects may require a dose reduction or discontinuation, thus limiting its clinical efficacy. Enteric-coated (EC) mycophenolate sodium is a new formulation of mycophenolic acid (MPA) that delivers the active moiety MPA, the same active moiety delivered by mycophenolate mofetil. It has been developed to help protect the upper gastrointestinal tract. It is implied that a reduction of adverse drug effects as well as a reduction of dose may improve efficacy and compliance. Noncompliance is often underestimated in solid organ transplant recipients, and adverse drug effects increase medication nonadherence. Recent clinical trials comparing EC mycophenolate sodium and mycophenolate mofetil in kidney recipients reported similar rates of efficacy and adverse effects. It is noteworthy that systemic MPA exposure is higher with EC mycophenolate sodium than with mycophenolate mofetil, without increased gastrointestinal toxicity. This finding is quite surprising, because part of MPA-associated gastrointestinal toxicity is related to its antiproliferative effect on enterocytes. However, enteric coating of MPA did not markedly reduce the number of gastrointestinal adverse effects. Further studies focusing on dosage, therapeutic drug monitoring and immunosuppressive regimens may reveal benefits of EC mycophenolate sodium for optimal individualised immunosuppression and improved compliance. At present, EC mycophenolate sodium is an alternative immunosuppressant to mycophenolate mofetil in kidney transplant recipients with an almost identical efficacy and safety profile.
Topics: Biological Availability; Humans; Mycophenolic Acid; Tablets, Enteric-Coated
PubMed: 15907141
DOI: 10.2165/00003495-200565080-00001 -
Expert Opinion on Pharmacotherapy Mar 2006The immunosuppressive agent mycophenolate mofetil has been successfully used over the past 10 years to prevent acute allograft rejection after renal transplantation. It... (Review)
Review
The immunosuppressive agent mycophenolate mofetil has been successfully used over the past 10 years to prevent acute allograft rejection after renal transplantation. It has mainly been administered as a fixed dose of mycophenolate mofetil 1000 mg b.i.d. The pharmacokinetics of mycophenolic acid, the active moiety of the prodrug mycophenolate mofetil, show large between-patient variability, and exposure to mycophenolic acid correlates with the risk for acute rejection. This suggests that already excellent clinical results can be further improved by mycophenolate mofetil dose individualization. This review discusses different arguments in favour of individualization of mycophenolate mofetil dose, as well as strategies for managing mycophenolate mofetil therapy individualization, including pharmacokinetic and pharmacodynamic monitoring and dose individualization based on pharmacogenetic information. It is expected that pharmacokinetic monitoring of mycophenolic acid will offer the most effective and feasible tool for mycophenolate mofetil dose individualization.
Topics: Dose-Response Relationship, Drug; Drug Monitoring; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid; Randomized Controlled Trials as Topic
PubMed: 16503809
DOI: 10.1517/14656566.7.4.361