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Transplantation Reviews (Orlando, Fla.) Jul 2009Recent attention has focused on individualizing mycophenolate mofetil therapy via monitoring of mycophenolic acid (MPA) levels to overcome interpatient variability in... (Review)
Review
BACKGROUND
Recent attention has focused on individualizing mycophenolate mofetil therapy via monitoring of mycophenolic acid (MPA) levels to overcome interpatient variability in MPA exposure when standard doses are administered. To our knowledge, no systematic review of the pharmacokinetic data in orthotopic heart transplant recipients has been published to date.
OBJECTIVE
The study aimed to systematically review published studies on the MPA target concentration that is effective at preventing rejection in cardiac transplant patients.
METHODOLOGY
A search of MEDLINE (January 1996 to July 2008) and EMBASE (January 1980 to July 2008) was conducted for articles describing the relationship between rejection and MPA concentration.
RESULTS
The literature search yielded 7 citations for inclusion: 1 prospective, randomized controlled study (level I); 2 prospective, nonrandomized controlled studies (level II-1); 1 well-designed cohort study (level II-2); 2 retrospective cohort studies (level II-3); and 1 case report (level III).
CONCLUSIONS
The relationship between MPA levels and rejection cannot be clearly defined based on available evidence. Preliminary evidence suggests limited sampling strategies may be a better predictor of rejection than a single-time point model. Further studies must be conducted on the relationship between the MPA area under the curve, the risk of rejection, and adverse effects to appreciate the value of such strategies.
Topics: Chromatography, High Pressure Liquid; Drug Monitoring; Graft Rejection; Heart Transplantation; Humans; Immunosuppressive Agents; Mycophenolic Acid
PubMed: 19345081
DOI: 10.1016/j.trre.2009.02.002 -
Ophthalmology Aug 2008To evaluate the outcomes of treatment with mycophenolate mofetil in patients with scleritis and uveitis refractory to or intolerant of methotrexate.
PURPOSE
To evaluate the outcomes of treatment with mycophenolate mofetil in patients with scleritis and uveitis refractory to or intolerant of methotrexate.
DESIGN
Retrospective noncomparative case series.
PARTICIPANTS
Eighty-five patients with scleritis and/or uveitis who failed with or did not tolerate methotrexate and were subsequently treated with mycophenolate mofetil between 1998 and 2006.
METHODS
We reviewed medical records of patients who were treated with mycophenolate mofetil after methotrexate intolerance or failure at one tertiary uveitis referral practice. We recorded dose and duration of methotrexate and mycophenolate mofetil therapy, inflammation grade, Snellen visual acuity (VA), use of other immunomodulatory therapy, and adverse events. Multivariate logistic regression was used to identify factors associated with inflammation control.
MAIN OUTCOME MEASURES
Control of inflammation, steroid-sparing effect, VA, and adverse effects were assessed.
RESULTS
Inflammation was controlled with mycophenolate mofetil in 47 patients (55%), with 5 achieving durable remission off all medication. In multivariate logistic regression analysis that adjusted for gender and age, the odds of inflammation control were lower for patients with scleritis (odds ratio [OR], 0.19; 95% confidence interval [CI], 0.04-0.93; P = 0.04) than for patients without scleritis. Among patients without scleritis, the odds of inflammation control were lower for patients with juvenile idiopathic arthritis (JIA)-associated uveitis (OR, 0.14; CI, 0.02-0.81, P = 0.03) compared to patients without JIA-associated uveitis. Eight of the 11 patients (73%) who were taking concomitant prednisone were able to taper their dose to <10 mg daily. Visual acuity declined in a greater percentage of patients who were unresponsive to mycophenolate mofetil (29%) compared with that of patients who responded to mycophenolate mofetil (9%). Side effects requiring discontinuation of mycophenolate mofetil occurred in 18 patients (21%).
CONCLUSIONS
Mycophenolate mofetil was effective in controlling inflammation in approximately half of the patients who had previously failed with or did not tolerate methotrexate. The odds of inflammation control were less in patients with the diagnoses of scleritis and JIA.
Topics: Adolescent; Adult; Child; Child, Preschool; Confidence Intervals; Female; Folic Acid Antagonists; Humans; Immunosuppressive Agents; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Odds Ratio; Retrospective Studies; Scleritis; Treatment Failure; Treatment Outcome; Uveitis; Visual Acuity
PubMed: 18221998
DOI: 10.1016/j.ophtha.2007.12.011 -
Clinical Pharmacokinetics 2002Adequate immunosuppression minimising the risk of organ rejection with acceptable tolerability of the used drugs is a crucial step in organ transplantation. The primary... (Review)
Review
Adequate immunosuppression minimising the risk of organ rejection with acceptable tolerability of the used drugs is a crucial step in organ transplantation. The primary goal is to maintain a consistent time-dependent target concentration by tailoring individual dosage leading to the best efficacy and tolerability combination. The use of therapeutic drug monitoring (TDM) to optimise immunosuppressive therapy is routinely employed for maintenance drugs such as cyclosporin and tacrolimus. The question whether therapeutic monitoring of mycophenolic acid (MPA) in organ transplant recipients treated with mycophenolate mofetil is necessary is not definitely answered. The correlation of mycophenolic acid pharmacokinetic parameters with efficacy and toxicity makes the therapeutic monitoring of this drug promising. However, further studies are mandatory to draw the best guidelines in order to achieve higher levels of evidence that MPA-TDM may improve patient outcome.
Topics: Drug Monitoring; Graft Rejection; Humans; Immunosuppressive Agents; Monitoring, Immunologic; Mycophenolic Acid
PubMed: 12036390
DOI: 10.2165/00003088-200241050-00001 -
Ophthalmology Aug 2005To evaluate treatment outcomes with mycophenolate mofetil in patients with inflammatory eye disease.
PURPOSE
To evaluate treatment outcomes with mycophenolate mofetil in patients with inflammatory eye disease.
DESIGN
Retrospective case series.
PARTICIPANTS
Eighty-four consecutive patients with inflammatory eye disease treated with mycophenolate mofetil at an academic referral center.
METHODS
Medical records were reviewed for treatment with mycophenolate mofetil. Dose of mycophenolate mofetil, response to therapy, dose of prednisone, use of other immunosuppressive drugs, and side effects associated with the use of mycophenolate mofetil were recorded.
MAIN OUTCOME MEASURES
Ability to control ocular inflammation with mycophenolate mofetil and to taper prednisone to < or =10 mg daily, and incidence of treatment-related side effects.
RESULTS
Of the 84 patients treated with mycophenolate mofetil, 61% had uveitis, 17% had scleritis, 11% had mucous membrane pemphigoid, and 11% had orbital or other inflammatory disease. Forty-three percent of patients treated with mycophenolate mofetil had been treated with at least one other immunosuppressive drug previously. The median dose of prednisone at the start of mycophenolate mofetil therapy was 40 mg, and 82% of the patients were considered a treatment success, as judged by the ability to control the inflammation and taper prednisone to < or =10 mg daily. Median time to treatment success was 3.5 months. Mycophenolate mofetil therapy was discontinued due to insufficient efficacy at a rate of 0.10 per person-year (PY) and due to side effects at a rate of 0.08/PY. The most frequent side effect was gastrointestinal upset, with a rate of 0.19/PY.
CONCLUSIONS
These data suggest that mycophenolate mofetil may be an effective corticosteroid-sparing agent in the treatment of inflammatory eye disease with a manageable side effect profile.
Topics: Adolescent; Adult; Aged; Child; Conjunctival Diseases; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Orbital Pseudotumor; Pemphigoid, Benign Mucous Membrane; Prednisone; Retrospective Studies; Scleritis; Treatment Outcome; Uveitis
PubMed: 16061096
DOI: 10.1016/j.ophtha.2005.02.020 -
Journal of the American Society of... Dec 2006Cardiovascular risk factors after kidney transplantation are enhanced as a result of the chronic use of immunosuppressants. Tacrolimus with mycophenolate mofetil has... (Review)
Review
Cardiovascular risk factors after kidney transplantation are enhanced as a result of the chronic use of immunosuppressants. Tacrolimus with mycophenolate mofetil has become the most commonly used combination after kidney transplantation. Cardiovascular risk factors that are related to the use of this combined therapy have been analyzed in various clinical trials in comparison with other immunosuppressive therapies. This review summarizes the main results of these studies regarding arterial hypertension, lipid profile, posttransplantation diabetes, renal function, and even acute rejection rate. The aim is to characterize the cardiovascular risk profile of tacrolimus and mycophenolate mofetil association when compared with older and newer immunosuppressive associations.
Topics: Cardiovascular Diseases; Drug Therapy, Combination; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid; Risk Factors; Tacrolimus
PubMed: 17130278
DOI: 10.1681/ASN.2006080930 -
Annals of Internal Medicine Mar 2000
Topics: Eczema, Dyshidrotic; Female; Foot Dermatoses; Hand Dermatoses; Humans; Immunosuppressive Agents; Middle Aged; Mycophenolic Acid
PubMed: 10691595
DOI: 10.7326/0003-4819-132-5-200003070-00015 -
Lupus 2001Mycophenolate mofetil is an immunosuppressive drug that is of established efficacy in renal transplantation. It inhibits the de novo pathway of purine synthesis and... (Review)
Review
Mycophenolate mofetil is an immunosuppressive drug that is of established efficacy in renal transplantation. It inhibits the de novo pathway of purine synthesis and therefore lymphocyte proliferation. Mycophenylate mofetil has been shown to ameliorate the severity of renal injury in murine models of lupus nephritis. Recent studies suggest that it may also be effective in the treatment of patients with lupus nephritis when used in conjunction with steroids. These observations need to be confirmed in adequately sized randomised-controlled studies.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Humans; Lupus Erythematosus, Systemic; Mycophenolic Acid
PubMed: 11315353
DOI: 10.1191/096120301673517315 -
The Journal of the Association of... Feb 2011The treatment of primary glomerular diseases is highly variable and is often complicated due to drug resistance, relapses and drug toxicity. Various immunosuppressive... (Review)
Review
The treatment of primary glomerular diseases is highly variable and is often complicated due to drug resistance, relapses and drug toxicity. Various immunosuppressive drugs have been tried, but there is as yet no superiority of any single drug. Mycophenolate mofetil is a relatively new drug which has shown some superiority in renal transplantation and lupus nephritis. It has an advantage of relatively less side effects with no nephrotoxicity. This article reviews the recent literature on the effect of this drug in managing primary glomerular diseases.
Topics: Glomerulonephritis; Humans; Immunosuppressive Agents; India; Mycophenolic Acid; Nephrotic Syndrome
PubMed: 21751645
DOI: No ID Found -
Clinical Journal of the American... Jul 2006
Topics: Acute Disease; Humans; Mycophenolic Acid; Nephritis, Interstitial
PubMed: 17699264
DOI: 10.2215/CJN.01020306 -
The Journal of Heart and Lung... 1994Mycophenolate mofetil (formerly known as RS-61443) is a morpholinoethyl ester of mycophenolic acid. Mycophenolic acid is a unique immunosuppressive agent because of its... (Clinical Trial)
Clinical Trial Review
Mycophenolate mofetil (formerly known as RS-61443) is a morpholinoethyl ester of mycophenolic acid. Mycophenolic acid is a unique immunosuppressive agent because of its mechanism of action. By inhibiting the de novo pathway of purine synthesis, mycophenolic acid suppresses lymphocyte function much more than that of neutrophil, erythrocyte, and other rapidly dividing cell lines which can use the salvage purine synthesis pathway. Mycophenolate mofetil has been shown to be an effective immunosuppressive agent in both animal models and early human trials. This article describes the history, biochemistry, pharmacology, in vitro and in vivo effects, and clinical trials of myophenolate mofetil. In addition, previously unpublished 3-year follow-up of heart transplant recipients receiving mycophenolate mofetil is reported.
Topics: Animals; Controlled Clinical Trials as Topic; Drug Therapy, Combination; Female; Graft Rejection; Heart Transplantation; Humans; Immunosuppressive Agents; In Vitro Techniques; Kidney Transplantation; Male; Middle Aged; Multicenter Studies as Topic; Mycophenolic Acid; Randomized Controlled Trials as Topic; Time Factors
PubMed: 7947873
DOI: No ID Found