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Handbook of Experimental Pharmacology 2020The goal of immunosuppressive therapy post-transplantation in pediatric renal transplant recipients is to prevent acute and chronic rejection while minimizing drug side...
The goal of immunosuppressive therapy post-transplantation in pediatric renal transplant recipients is to prevent acute and chronic rejection while minimizing drug side effects. Most therapies alter immune response mechanisms but are not immunologically specific, and a careful balance is required to find the dose that prevents rejection of the graft while minimizing the risks of overimmunosuppression leading to infection and cancer. While this chapter because of space constraints focuses on immunosuppressive therapy in pediatric renal transplant recipients, many aspects can be applied on pediatric recipients of other solid organ transplants such as the liver and heart. The major maintenance immunosuppressive agents currently used in various combination regimens are tacrolimus, cyclosporine, mycophenolate mofetil, azathioprine, everolimus, sirolimus, and glucocorticoids (steroids). Although data from adult renal transplantation trials are used to help guide management decisions in pediatric patients, immunosuppressive therapy in pediatric renal transplant recipients often must be modified because of the unique dosage requirements and clinical effects of these agents in children, including their impact on growth and development. The optimal immunosuppressive therapy post-transplant is not established. The goal remains to find the best combination of immunosuppressive agents that optimizes allograft survival by preventing acute rejection while limiting drug toxicities.
Topics: Adult; Child; Cyclosporine; Drug Therapy, Combination; Graft Rejection; Humans; Immunosuppressive Agents; Mycophenolic Acid; Tacrolimus
PubMed: 31820175
DOI: 10.1007/164_2019_331 -
Clinical and Experimental Dermatology Oct 2002In the past decade, there has been enormous progress in the understanding of the pathomechanisms of immune-mediated diseases, which has led to major advances in... (Review)
Review
In the past decade, there has been enormous progress in the understanding of the pathomechanisms of immune-mediated diseases, which has led to major advances in immunotherapeutic strategies. As a consequence, the armamentarium of specific and nonspecific immune-modulating and immunosuppressive drugs for the treatment of skin diseases has been widely extended. Among the nonspecific immunomodulators, mycophenolate mofetil and leflunomide show promising effects in a variety of autoimmune and inflammatory skin disorders. Both compounds inhibit a key enzyme in nucleotide biosynthesis, a step that is pivotal for the production of cytotoxic T cells and antibody formation. They do not act in the nucleus, which may explain their advantageous side-effect profile.
Topics: Administration, Oral; Autoimmune Diseases; Female; Fertility; Fetal Death; Humans; Immunosuppressive Agents; Infertility, Male; Isoxazoles; Leflunomide; Male; Mycophenolic Acid; Pregnancy; Skin Diseases
PubMed: 12464151
DOI: 10.1046/j.1365-2230.2002.01150.x -
The Netherlands Journal of Medicine Dec 2000Mycophenolate mofetil is a new immunosuppressive drug, exhibiting its effect through inhibition of proliferation of T- and B-lymphocytes. Superior efficacy of... (Review)
Review
Mycophenolate mofetil is a new immunosuppressive drug, exhibiting its effect through inhibition of proliferation of T- and B-lymphocytes. Superior efficacy of mycophenolate mofetil compared to azathioprine, in combination with cyclosporine and prednisone, in the prevention of acute rejection in organ transplantation has made mycophenolate mofetil one of the standard immunosuppressive drugs after transplantation. Mycophenolate mofetil also is an interesting candidate drug for many other, mainly auto-immune mediated diseases. The use of mycophenolate mofetil in several of these diseases is discussed. The definitive place of mycophenolate mofetil will depend on the results of randomised trials currently under way.
Topics: Autoimmune Diseases; Graft Rejection; Humans; Immunosuppressive Agents; Internal Medicine; Male; Mycophenolic Acid; Randomized Controlled Trials as Topic; Sensitivity and Specificity; Transplantation Immunology
PubMed: 11099793
DOI: 10.1016/s0300-2977(00)00069-3 -
BioDrugs : Clinical Immunotherapeutics,... 2001Mycophenolate mofetil (MMF) is an immunosuppressive drug designed to inhibit inosine monophosphate dehydrogenase (IMPDH). IMPDH is a key enzyme in the de novo purine... (Review)
Review
Mycophenolate mofetil (MMF) is an immunosuppressive drug designed to inhibit inosine monophosphate dehydrogenase (IMPDH). IMPDH is a key enzyme in the de novo purine synthesis of lymphocytes. It is crucially important for proliferative responses of human T and B lymphocytes. The inhibition of IMPDH thus leads to selective lymphocyte suppression. After successful use in various in vitro and animal models, MMF was brought to clinical trial in patients undergoing transplantation. The drug is rapidly and completely absorbed following oral administration. Pilot studies of administration with cyclosporin and corticosteroids suggested a significant reduction in the incidence of organ rejection at dosages of 1 to 3 g/day. As a result of these studies, 3 pivotal randomised double-blind multicentre trials, involving nearly 1500 patients, were designed to investigate the effects of addition of MMF to different standard immunosuppressive protocols on the prevention of acute renal allograft rejection. After 6 months, the rates of biopsy-proven rejection were significantly reduced in patients receiving MMF. In combination with cyclosporin and corticosteroids, the adverse effect profile resembled that of azathioprine. Most adverse effects were associated with the gastrointestinal tract, the blood system and opportunistic infections. MMF offers improved immunosuppressive therapy following renal and probably other solid organ transplantation. MMF has been licensed since 1995 for the prevention of acute renal allograft rejection in most countries. It has been used in different combinations of immunosuppressive drugs and in various dosages and regimens.
Topics: Animals; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid
PubMed: 11437674
DOI: 10.2165/00063030-200115010-00004 -
Expert Opinion on Drug Metabolism &... Oct 2005Mycophenolate mofetil (MMF) received its first approval for the prevention of renal allograft rejection in 1995 and has now become the most frequently used... (Review)
Review
Mycophenolate mofetil (MMF) received its first approval for the prevention of renal allograft rejection in 1995 and has now become the most frequently used antiproliferative agent in maintenance immunosuppressive therapy for kidney, pancreas, liver and heart transplantation. In addition, its use for the treatment of autoimmune diseases steadily increases. This review focuses on the miscellaneous pharmacodynamic properties of the drug, its pharmacokinetics in healthy subjects, recipients of different organ transplants and combination therapy with other pharmaceuticals, as well as its safety profile. The immunosuppressive activity of MMF is thought to derive mainly from the potent and selective inhibition of purine synthesis in both T and B lymphocytes. In contrast to other immunosuppressants on the market, it is metabolised primarily by glucuronidation and lacks nephrotoxicity, cardiovascular toxicity or diabetogenic potential, thus making it a suitable candidate for combination regimens. The most important side effects under MMF include gastrointestinal disorders, of which the underlying mechanisms are not yet fully understood, but seem to be complex and related to both effects of mycophenolic acid and its acyl glucuronide, as well as to decreased -immunity due to general immunosuppression after transplantation.
Topics: Animals; Drug Interactions; Food-Drug Interactions; Humans; Immunosuppressive Agents; Mycophenolic Acid; Organ Transplantation; Transplantation Immunology
PubMed: 16863458
DOI: 10.1517/17425255.1.3.505 -
Journal of Hepatology Sep 2000
Review
Topics: Hepatitis, Autoimmune; Humans; Immunosuppressive Agents; Mycophenolic Acid
PubMed: 11020006
DOI: 10.1016/s0168-8278(00)80286-x -
Lupus 2005The systemic vasculitides are a group of potentially life-threatening multi-system autoimmune connective tissue diseases characterized by vascular inflammation. The gold... (Review)
Review
The systemic vasculitides are a group of potentially life-threatening multi-system autoimmune connective tissue diseases characterized by vascular inflammation. The gold standard therapies include corticosteroids and cyclophosphamide as induction therapy and other agents such as azathioprine and methotrexate to maintain remission. Mycophenolate mofetil (MMF) is increasingly being used in autoimmune disorders and this article reviews the use of this agent in the systemic vasculitides.
Topics: Antibodies, Antineutrophil Cytoplasmic; Humans; Immunosuppressive Agents; Mycophenolic Acid; Vasculitis
PubMed: 15803934
DOI: 10.1191/0961203305lu2120oa -
Lupus 2005Mycophenolate mofetil (MMF) is an immunosuppressive drug the efficiency of which has been established in renal transplantation. Recent studies suggest that it may also... (Review)
Review
Mycophenolate mofetil (MMF) is an immunosuppressive drug the efficiency of which has been established in renal transplantation. Recent studies suggest that it may also be effective in the treatment of variant skin diseases especially if the skin lesions are triggered by lymphocytes. Studies have shown efficacy in autoimmune bullous dermatoses, atopic dermatitis and psoriasis. However, there are no placebo-controlled trials that support the use of MMF as first line therapy in these skin diseases.
Topics: Dermatitis, Atopic; Humans; Immunosuppressive Agents; Lupus Erythematosus, Cutaneous; Mycophenolic Acid; Psoriasis; Pyoderma Gangrenosum; Skin Diseases, Vesiculobullous
PubMed: 15803935
DOI: 10.1191/0961203305lu2121oa -
Lupus 2005Mycophenolate mofetil (MMF) initially found widespread use in the immunoprophylaxis of rejection in organ transplantation. It has subsequently been used in lupus... (Review)
Review
Mycophenolate mofetil (MMF) initially found widespread use in the immunoprophylaxis of rejection in organ transplantation. It has subsequently been used in lupus glomerulonephritis, where early studies have shown it to be effective in induction and maintenance therapy. The randomized studies have mostly studied small groups of patients and their conclusions do need to be confirmed in larger studies. MMF has also been used in small numbers of patients in a variety of nonlupus glomerulopathies, which have different underlying immunopathology as well as clinical course, including IgA nephropathy, membranous nephropathy, focal segmental glomerulosclerosis, membranoproliferative glomerulonephritis, hepatitis-C-associated glomerulonephritis and even Goodpasture's syndrome. In this article, we discuss its use in such nonlupus glomerular diseases.
Topics: Glomerulonephritis; Humans; Immunosuppressive Agents; Mycophenolic Acid
PubMed: 15803930
DOI: 10.1191/0961203305lu2116oa -
Annals of Allergy, Asthma & Immunology... Jan 2003This article should familiarize the reader with the pharmacokinetics, mechanisms of action, potential toxicities, and current and future applications of mycophenolate... (Review)
Review
OBJECTIVES
This article should familiarize the reader with the pharmacokinetics, mechanisms of action, potential toxicities, and current and future applications of mycophenolate mofetil.
DATA SOURCES
The current medical literature.
RESULTS
Mycophenolate mofetil is an immunosuppressive agent that has been used for transplant recipients. More recently, this agent has been used to treat several inflammatory conditions.
CONCLUSIONS
Mycophenolate mofetil has the potential to be a useful agent in the treatment of several inflammatory conditions, including systemic lupus erythematosus.
Topics: Autoimmune Diseases; Dose-Response Relationship, Drug; Forecasting; Humans; Immunosuppressive Agents; Inflammation; Mycophenolic Acid; Risk Factors
PubMed: 12546332
DOI: 10.1016/S1081-1206(10)63607-1