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Pharmacotherapy 1997Mycophenolate mofetil is the morpholinoethylester prodrug of mycophenolic acid, an agent that inhibits the proliferation of B and T lymphocytes through noncompetitive,... (Review)
Review
Mycophenolate mofetil is the morpholinoethylester prodrug of mycophenolic acid, an agent that inhibits the proliferation of B and T lymphocytes through noncompetitive, reversible inhibition of inosine monophosphate dehydrogenase, a key enzyme in the de novo synthetic pathway of guanine nucleotides. Currently, mycophenolate mofetil is approved for the prevention of acute renal allograft rejection when given in combination with cyclosporine and steroids. Several studies also demonstrated that the agent is effective in the treatment of refractory rejection in renal, heart, and liver transplant recipients, and may have efficacy in the treatment of chronic rejection as well.
Topics: Animals; Arthritis, Rheumatoid; Graft Rejection; Humans; Immunosuppressive Agents; Intestinal Absorption; Mycophenolic Acid
PubMed: 9399601
DOI: No ID Found -
Dermatologic Therapy 2007Mycophenolate mofetil (MMF) is a relatively new systemic immunosuppressive agent whose use is rapidly increasing within the field of dermatologic. Originally used in the... (Review)
Review
Mycophenolate mofetil (MMF) is a relatively new systemic immunosuppressive agent whose use is rapidly increasing within the field of dermatologic. Originally used in the 1970s for the treatment of psoriasis, MMF has demonstrated efficacy in multiple types of inflammatory skin diseases. Although the safety data within the dermatologic literature is sparse, MMF's extensive use within the field of organ transplantation has demonstrated a favorable safety profile. MMF's lack of hepatic or renal toxicity is a significant advantage over immunosuppressive medications currently used in dermatology and make MMF an attractive candidate for multidrug regimens. In this review the present authors discuss the pharmacology, mechanisms of action, side effects and current uses of MMF reported within the dermatologic literature. The present authors also provide practical information regarding the use of the MMF culled from the literature as well as from the present authors' own clinical experience with the medication.
Topics: Animals; Connective Tissue Diseases; Drug Interactions; Humans; Immunosuppressive Agents; Mycophenolic Acid; Pemphigus; Psoriasis; Skin Diseases
PubMed: 17970888
DOI: 10.1111/j.1529-8019.2007.00136.x -
Lancet (London, England) Nov 1996
Review
Topics: Drug Interactions; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid
PubMed: 8918281
DOI: 10.1016/S0140-6736(96)10310-X -
Clinical Journal of the American... Sep 2020
Topics: Humans; Immunosuppressive Agents; Kidney Diseases; Mycophenolic Acid
PubMed: 32841154
DOI: 10.2215/CJN.11740720 -
Kidney International. Supplement Dec 1995Mycophenolate mofetil (MMF), the morpholinoethyl ester of mycophenolic acid (MPA), is a new selective immunosuppressant used for the prevention and treatment of acute... (Review)
Review
Mycophenolate mofetil (MMF), the morpholinoethyl ester of mycophenolic acid (MPA), is a new selective immunosuppressant used for the prevention and treatment of acute renal rejection after transplantation. In vivo MMF is deesterified to MPA, which is a potent and specific inhibitor of de novo purine synthesis and suppressor of both T and B lymphocyte proliferation. In animal studies, MMF has been shown to be effective in prolonging the survival of allografts and xenografts in rodents, dogs, and monkeys. Experimental evidence in animal models suggests that MMF also may be effective in the treatment of chronic vascular rejection. A phase I clinical trial showed MMF was well tolerated in renal transplant patients at doses up to 3,500 mg/day for up to two years. There was no correlation between the incidence of adverse effects and dose of MMF, and no overt nephrotoxicity, hepatotoxicity, or myelotoxicity was observed. In a multicenter study in patients with biopsy-proven renal allograft rejection, successful rescue (stabilization or improvement of renal function) was achieved with MMF in combination with maintenance doses of cyclosporine and prednisone in 69% of patients. This result suggested that MMF may be effective in the treatment of renal allograft rejection after transplantation. In a large multicenter trial, MMF in combination with cyclosporine and prednisone was superior to a standard immunosuppressive regimen including azathioprine. Taken together, the data indicate that MMF will be a valuable addition to the list of immunosuppressants available for the prevention and treatment of renal rejection after transplantation.
Topics: Animals; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid
PubMed: 8587275
DOI: No ID Found -
Current Opinion in Rheumatology May 2021Although mycophenolate mofetil (MMF) has been used successfully to treat a myriad of autoimmune diseases, its complex pharmacokinetics make it difficult to determine the... (Review)
Review
PURPOSE OF REVIEW
Although mycophenolate mofetil (MMF) has been used successfully to treat a myriad of autoimmune diseases, its complex pharmacokinetics make it difficult to determine the true drug exposure for an individual patient. This review summarizes the body of literature focused on the gold standard measurement of the area under the curve (AUC) of mycophenolic acid (MPA), the active metabolite of MMF.
RECENT FINDINGS
Fixed dosing of MMF leads to highly variable drug exposure. Retrospective series have reported improved clinical outcomes when a minimum AUC value from 0 to 12 h (AUC0-12h) ≥30 mg h/l is achieved. MPA levels are affected by various drug interactions, hypoalbuminemia, and renal insufficiency and the measurement of free rather than total MPA levels is prudent in some situations. A limited number of studies employing prospective dose adjustment of MMF based on AUC0-12h measurements have yielded mixed results.
SUMMARY
Given the wide range of MPA AUC encountered in autoimmune diseases, dose adjustments of MMF based on AUC rather than fixed dosing of MMF should be considered in both clinical practice and clinical trials. Limited sampling strategies have been proposed to improve clinical feasibility of measurements, but a standard is yet to be defined.
Topics: Area Under Curve; Autoimmune Diseases; Humans; Immunosuppressive Agents; Mycophenolic Acid
PubMed: 33741807
DOI: 10.1097/BOR.0000000000000799 -
Journal of the American Academy of... Feb 2009Mycophenolate mofetil (MMF) is the prodrug of mycophenolic acid (MPA), a medication used to treat psoriasis in the 1970s until side effects and the concern of... (Review)
Review
UNLABELLED
Mycophenolate mofetil (MMF) is the prodrug of mycophenolic acid (MPA), a medication used to treat psoriasis in the 1970s until side effects and the concern of carcinogenesis led to its discontinuation. The prodrug, MMF, emerged decades later in the transplant field. Dermatologists have since used MMF off-label to treat various inflammatory skin conditions, with most research concentrating on its use in psoriasis, autoimmune blistering disorders, dermatitides, and connective tissue disorders. The appeal of MMF is predicated upon its lymphocyte specificity and consequent decreased toxicity profile. These attributes may make it a preferable treatment option. Its use in the field of dermatology is currently limited by a lack of randomized controlled trials, potential unknown side effects, and cost of treatment. In reviewing both current literature and our own clinic records, MMF appears to be a promising therapeutic option for the treatment of cutaneous inflammatory diseases.
LEARNING OBJECTIVE
After completing this learning activity, participants should be able to summarize the history and pharmacology of mycophenolate mofetil as an immunosuppressant; recognize its potential role in the treatment of dermatologic conditions, including general dosing guidelines, use in pregnancy and pediatrics, and potential adverse effects; and identify future considerations and developing areas of research regarding the use of mycophenolate mofetil in dermatology.
Topics: Dermatology; Education, Medical, Continuing; Humans; Immunosuppressive Agents; Mycophenolic Acid; Skin Diseases
PubMed: 19150270
DOI: 10.1016/j.jaad.2008.08.049 -
Drugs of Today (Barcelona, Spain : 1998) Jul 2009Mycophenolic acid (MPA) is a potent, selective, noncompetitive and reversible inhibitor of inosine-5'-monophosphate deshydrogenase (IMPDH). By depleting guanosine and... (Review)
Review
Mycophenolic acid (MPA) is a potent, selective, noncompetitive and reversible inhibitor of inosine-5'-monophosphate deshydrogenase (IMPDH). By depleting guanosine and deoxyguanosine nucleotides in T and B lymphocytes it inhibits their proliferation and, hence, immunoglobin (Ig) production. MPA also suppresses dendritic cell maturation decreasing its capacity of antigen presentation to T lymphocytes. MPA reduces the recruitment of monocytes into sites of graft rejection and inflammation. Mycophenolate mofetil (MMF) is a prodrug of MPA that was developed to improve the bioavailability of MPA. After oral administration, MMF is completely metabolized to MPA. A major inactive metabolite, mycophenolic acid glucuronide (MPAG), is formed after MPA glucuronidation. MPAG has an important role in the enterohepatic recirculation of MPA. MMF is approved for the prophylaxis of allograft rejection after renal, cardiac or liver transplant. The oral dose ranges from 1.0-1.5 g/day twice daily. Moreover, studies on the use of MMF in lung and simultaneous pancreas/ kidney transplants have shown encouraging results. MMF also demonstrates potential in the treatment of autoimmune diseases such as lupus, myasthenia gravis and glomerular disorders. This review focuses on the molecular mechanism of action and pharmacological characteristics of MPA. Studies in both approved and nonapproved applications are also summarized.
Topics: Animals; Clinical Trials as Topic; Drug Evaluation, Preclinical; Humans; Immunosuppressive Agents; Mycophenolic Acid; Organ Transplantation; Prodrugs
PubMed: 19834629
DOI: 10.1358/dot.2009.45.7.1384878 -
Kidney International Jan 2008Mycophenolate mofetil is an immunosuppressive agent that blocks purine biosynthesis, inhibits T and B-lymphocyte and mesangial proliferation. Mycophenolate mofetil is... (Review)
Review
Mycophenolate mofetil is an immunosuppressive agent that blocks purine biosynthesis, inhibits T and B-lymphocyte and mesangial proliferation. Mycophenolate mofetil is not nephrotoxic like calcineurin inhibitors and is widely used in solid-organ transplantation. Recently, mycophenolate mofetil has been introduced in the treatment of autoimmune diseases and primary glomerulopathies. This review analyzes the literature currently available on the treatment of primary glomerulopathies with mycophenolate mofetil. Encouraging results have been obtained in minimal change nephropathy where it may help to reduce the use of steroids in these patients who are often very young. The results obtained in medium and high risk patients with focal segmental glomerulonephritis and idiopathic membranous nephropathy were less encouraging. Conflicting results have been reported on IgA nephropathy in controlled trials. None of these studies attained level A evidence, meaning that randomized control trials of sufficient statistical significance are necessary to estimate the real effectiveness of mycophenolate mofetil in primary glomerulopathies.
Topics: Glomerulonephritis, IGA; Glomerulonephritis, Membranous; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppressive Agents; Mycophenolic Acid; Nephrosis, Lipoid
PubMed: 17989649
DOI: 10.1038/sj.ki.5002653 -
Annals of Transplantation Dec 2013Liver transplantation is the only live-saving, curative treatment for various end-stage liver diseases, and it has excellent survival rates. Mycophenolate mofetil is... (Review)
Review
Liver transplantation is the only live-saving, curative treatment for various end-stage liver diseases, and it has excellent survival rates. Mycophenolate mofetil is widely used as co-medication for immunosuppression after liver transplantation, especially to allow a sparing effect on calcineurin-inhibitors, thus reducing their numerous adverse effects. It improves both graft and patient survival. The properties of its active metabolite, mycophenolic acid, are diverse: inhibition of de novo purine synthesis and selective lymphocyte inhibition, anti-tumoral, antiviral, anti-angioneoplastic, and vasculoprotective mechanisms are described and summarized in this review. The most common adverse effects of mycophenolate mofetil are gastrointestinal complaints such as diarrhea, which often lead to dose-reduction or withdrawal of mycophenolate mofetil. A newer, enteric-coated formulation is available, which is meant to reduce the gastrointestinal adverse effects. Mycophenolate mofetil does not relevantly interact with other common drugs. The question of whether therapeutic drug monitoring allows optimized dosing strategies cannot be satisfyingly answered yet. The optimal partner-immunosuppressant seems to be tacrolimus, especially in low doses. This tutorial review provides an overview of recent studies exploring the role of mycophenolate mofetil in liver transplantation with regards to its development, mechanism of action, and actual controversies such as therapeutic drug monitoring or de novo malignancy after transplantation.
Topics: End Stage Liver Disease; Humans; Immunosuppressive Agents; Liver Transplantation; Mycophenolic Acid; Treatment Outcome
PubMed: 24346057
DOI: 10.12659/AOT.889299