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Gastroenterology Clinics of North... Jun 2004In the past decade, immunosuppressive drugs have come to play an integral role in the treatment of patients with inflammatory bowel disease. Cyclosporine, microemulsion... (Review)
Review
In the past decade, immunosuppressive drugs have come to play an integral role in the treatment of patients with inflammatory bowel disease. Cyclosporine, microemulsion cyclosporine, tacrolimus, and mycophenolate mofetil can be considered for the treatment of patients with refractory inflammatory Crohn's disease, fistulizing Crohn's disease, and severe ulcerative colitis. This article reviews the use of cyclosporine, tacrolimus, and mycophenolate mofetil in patients with inflammatory bowel disease, with emphasis on pharmacology, results in controlled clinical trials, and safety, and issues related to dosing and toxicity monitoring.
Topics: Cyclosporine; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Mycophenolic Acid; Tacrolimus
PubMed: 15177532
DOI: 10.1016/j.gtc.2004.02.001 -
Transplantation Feb 2005Transplant coronary artery disease and malignancy are the major limitations to survival after heart transplantation. In a randomized trial, mycophenolate mofetil (MMF)... (Review)
Review
Transplant coronary artery disease and malignancy are the major limitations to survival after heart transplantation. In a randomized trial, mycophenolate mofetil (MMF) significantly improved 3-year survival over azathioprine, but the expected reduction in intracoronary ultrasound evidence of vasculopathy was not found on initial analysis using unmatched sites. On reanalysis using matched sites, a highly significant reduction in maximum intimal thickness was shown with MMF. Malignancy was numerically but not significantly lower at 3 years; in open label experience up to 7 years, it is diminished by 37% on MMF. MMF protects heart transplant recipients against both vasculopathy and malignancy.
Topics: Drug Therapy, Combination; Heart Transplantation; Humans; Immunosuppressive Agents; Mycophenolic Acid; Postoperative Complications; Survivors
PubMed: 15699750
DOI: 10.1097/01.tp.0000153302.27299.16 -
Transplantation Feb 2005The results of clinical trials of mycophenolate mofetil (MMF) and the analysis of numerous data from renal transplant registries have shown that MMF reduces the... (Review)
Review
The results of clinical trials of mycophenolate mofetil (MMF) and the analysis of numerous data from renal transplant registries have shown that MMF reduces the incidence of early and late rejection (even in the black population), is protective against long-term deterioration of renal function, and reduces late renal allograft loss independently of acute rejection without increasing the risk for malignancies.
Topics: Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid
PubMed: 15699751
DOI: 10.1097/01.tp.0000153303.53900.83 -
Immunopharmacology May 2000With the development of new immunosuppressive agents, the focus of anti-rejection therapy has shifted from prevention of acute allograft rejection to an emphasis on... (Review)
Review
With the development of new immunosuppressive agents, the focus of anti-rejection therapy has shifted from prevention of acute allograft rejection to an emphasis on sufficient immunosuppression with minimal toxicity. Mycophenolate mofetil (MMF) is a recently developed immunosuppressive drug, which acts to inhibit T and B cell proliferation by blocking the production of guanosine nucleotides required for DNA synthesis. It also prevents the glycosylation of adhesion molecules that are involved in attachment of lymphocytes to endothelium and potentially in leukocyte infiltration of an allograft during an immune response. High-quality randomized clinical trials have demonstrated that MMF, when used with cyclosporine (CsA) and steroids, reduces the frequency and severity of acute rejection episodes in kidney and heart transplants, improves patient and graft survival in heart allograft recipients and increases renal allograft survival at 3 years. It has also been effective in reversing acute and resistant rejection episodes in heart, kidney and liver recipients. The ability of MMF to facilitate sparing of other immunosuppressive agents, particularly in CsA-related nephrotoxicity, is also promising. By permitting reduction in CsA doses, MMF may stabilize or improve renal graft function in patients with CsA-related nephrotoxicity or chronic allograft nephropathy. Early results of phase I and II trials evaluating MMF therapy in liver and combined pancreas/kidney transplant recipients are encouraging. The main adverse effects associated with oral or intravenous MMF are gastrointestinal and hematologic in nature. Although the direct costs of using MMF vs. azathioprine (AZA) are higher, the decreased incidence and treatment of acute rejection in patients treated with MMF supports its use as a cost-effective option during the first year following transplantation.Thus, MMF has become an important therapeutic tool in the transplant clinician's armamentarium. Ongoing issues to be resolved in clinical trials include the role of MMF in the absence of other potent agents, e.g., as monotherapy or with a steroid but without calcineurin inhibitor; whether MMF will have an impact on chronic allograft dysfunction; and the cost-effectiveness of treatment following the first year of transplantation.
Topics: Animals; Graft Rejection; Humans; Immunosuppressive Agents; Mycophenolic Acid; Organ Transplantation; Purines; Signal Transduction; T-Lymphocytes
PubMed: 10878291
DOI: 10.1016/s0162-3109(00)00190-9 -
JAMA Neurology Nov 2014
Topics: Female; Humans; Male; Mycophenolic Acid; Neuromyelitis Optica
PubMed: 25199689
DOI: 10.1001/jamaneurol.2014.2359 -
American Journal of Transplantation :... Feb 2005
Topics: Graft Rejection; Humans; Immunosuppressive Agents; Mycophenolic Acid
PubMed: 15643976
DOI: 10.1111/j.1600-6143.2005.00793.x -
Transplantation Reviews (Orlando, Fla.) Jan 2014Since its regulatory approval in 1995, mycophenolate mofetil (MMF) has largely replaced azathioprine (AZA) as the anti-metabolite immunosuppressive of choice in kidney... (Review)
Review
Since its regulatory approval in 1995, mycophenolate mofetil (MMF) has largely replaced azathioprine (AZA) as the anti-metabolite immunosuppressive of choice in kidney transplantation. While the initial industry-sponsored clinical trials suggested strong reductions in the incidence of acute rejection in the first six months post transplantation, long-term follow-up studies have failed to demonstrate a similar degree of benefit in overall graft and patient survival. In addition, several subsequent studies have raised questions on the potential attenuating effects of calcineurin inhibitor choice on MMF efficacy when compared to AZA. This review will revisit the question of whether the available evidence continues to support the superiority of MMF over AZA in kidney transplantation outcomes while comprehensively reviewing the available evidence from clinical trial data, systematic reviews, and registry studies.
Topics: Clinical Trials as Topic; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid
PubMed: 24321304
DOI: 10.1016/j.trre.2013.10.005 -
Pediatric Nephrology (Berlin, Germany) Sep 2004Within a short period, we have witnessed a dramatic increase in the use of mycophenolate mofetil (MMF) in pediatric renal transplantation, with the drug often replacing... (Review)
Review
Within a short period, we have witnessed a dramatic increase in the use of mycophenolate mofetil (MMF) in pediatric renal transplantation, with the drug often replacing azathioprine in combination with calcineurin inhibitor therapy. When the drug was introduced, the manufacturer considered therapeutic drug monitoring (TDM) unnecessary. However, TDM studies revealed substantial inter- and intra-individual variability and drug interactions. There is a substantial drug interaction between MMF and cyclosporine, and lower doses are required in combination with tacrolimus (~500-800 mg/m(2) per day) than with cyclosporine (~1,200 mg/m(2) per day). Patients with autoimmune disease require an intermediate dose when receiving no concomitant calcineurin inhibitor (~900 mg/m(2) per day). It has been possible to detect drug interactions and to minimize adverse events only with TDM. This is especially important with increasing use of combination therapies. Pharmacodynamic monitoring (measuring the biological response to a drug) coupled with pharmacokinetics allow optimization of drug dosing, with maximum efficacy and minimal toxicity. More work is required to establish specific target ranges with the various drug combinations--especially for the pediatric population.
Topics: Child; Drug Monitoring; Humans; Immunosuppressive Agents; Mycophenolic Acid
PubMed: 15257455
DOI: 10.1007/s00467-004-1571-4 -
Modern Rheumatology Nov 2019This study aimed to determine the association between the dosage and pharmacokinetics of mycophenolate mofetil (MMF) in juvenile patients with autoimmune diseases....
This study aimed to determine the association between the dosage and pharmacokinetics of mycophenolate mofetil (MMF) in juvenile patients with autoimmune diseases. Totally, 29 patients were administered oral MMF. The blood concentrations of mycophenolate acid (MPA) at seven points, the area under the time-concentration curve (MPA-AUC), the peak concentration (), and the time to peak concentration () were measured. To obtain a dose-normalized MPA-AUC value, the actual measured MPA-AUC value was divided by the dose value of the morning administration corrected for body weight (BW) or body surface area (BSA). The patients were classified into three age groups (group 1, ≤10 years; group 2, >10-≤15 years; and group 3, >15 years), and pharmacokinetic parameters were compared among the groups. In total, we obtained 37 measurements. The actual measured MPA-AUC values and the MPA-AUC values corrected for dose per BW and were lower in young patients. The MPA-AUC values corrected for dose per BSA and were comparable among all the groups. In patients with juvenile autoimmune diseases, determining MMF administration dosage according to BSA may facilitate MPA-AUC value prediction.
Topics: Adolescent; Autoimmune Diseases; Child; Enzyme Inhibitors; Female; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Young Adult
PubMed: 30289014
DOI: 10.1080/14397595.2018.1532785 -
Transplantation Proceedings 2005Mycophenolate mofetil (MMF) is an immunosuppressive drug, exhibiting its effect through inhibition of proliferation of T and B lymphocytes. Standard primary... (Review)
Review
Mycophenolate mofetil (MMF) is an immunosuppressive drug, exhibiting its effect through inhibition of proliferation of T and B lymphocytes. Standard primary immunosuppressive therapy after orthotopic liver transplantation (OLT) is based on a calcineurin-inhibitor (CNI): cyclosporine or tacrolimus. Renal failure with arterial hypertension, due to CNI side-effects, is a major cause of morbidity and mortality after OLT. Several studies have shown the efficacy of MMF to improve CNI-induced nephrotoxicity, blood pressure, and uric acid concentration in liver transplant patients with concomitant reduction or withdrawal of CNI. Predose plasma mycophenolic acid concentrations (MPA) are related to adverse events, drug dose, and clinical status. Blood level values outside the suggested MPA therapeutic range are associated with acute rejection episodes and side effects, which have been described in about half of the patients treated with MMF. Most authors have described gastrointestinal and hematological side-effects, whereas these appear usually dose related, responding quickly to reduction. MMF is potent and safe immunosuppressive agent, and replacement of CNI by MMF in liver transplant patients with renal dysfunction may improve not only kidney function but also other CNI-associated side-effects, such as hypertension and hyperuricemia, with a low risk of rejection.
Topics: B-Lymphocytes; Humans; Immunosuppressive Agents; Kidney; Liver Transplantation; Lymphocyte Activation; Mycophenolic Acid; T-Lymphocytes
PubMed: 16182764
DOI: 10.1016/j.transproceed.2005.06.073