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Clinical Transplantation Dec 2020The therapeutic drug monitoring of mycophenolic acid (MPA) has been investigated for renal and heart transplantations; however, its usefulness in lung transplantation is...
BACKGROUND
The therapeutic drug monitoring of mycophenolic acid (MPA) has been investigated for renal and heart transplantations; however, its usefulness in lung transplantation is unclear.
METHODS
The MPA area under the plasma concentration-time curve (AUC) was calculated in 59 adult lung transplant recipients. The MPA AUC s were compared among the three groups determined by the presence of adverse events (no events, infection, and chronic lung allograft dysfunction [CLAD]). Next, MPA AUC thresholds for the adverse events were identified by receiver operating characteristic analysis. Cumulative occurrence rate of the adverse events was compared between two groups (adequate and inadequate groups) according to the thresholds.
RESULTS
The MPA AUC s in the no event, infection, and CLAD groups were 30.3 ± 6.5, 36.8 ± 10.7, and 20.6 ± 9.6 µg·h/mL, respectively (P = .0027), while the tacrolimus trough levels were similarly controlled in the groups. The thresholds of MPA AUC for the occurrence of infection and CLAD were 40.5 and 22.8 µg·h/mL, respectively. The cumulative occurrence rate of adverse events of adequate group (15.3%) was significantly lower than that of inadequate group (56.0%) (P = .0050).
CONCLUSIONS
The MPA AUC may affect the occurrence of adverse events in lung transplant recipients.
Topics: Adult; Area Under Curve; Humans; Immunosuppressive Agents; Kidney Transplantation; Lung Transplantation; Mycophenolic Acid; Tacrolimus
PubMed: 32949050
DOI: 10.1111/ctr.14088 -
Clinical Transplantation Jul 2021Diarrhea is a well-known side effect of mycophenolic acid (MPA) use in kidney transplant recipients (KTRs). It is unknown whether self-reported diarrhea using the...
BACKGROUND
Diarrhea is a well-known side effect of mycophenolic acid (MPA) use in kidney transplant recipients (KTRs). It is unknown whether self-reported diarrhea using the Modified Transplant Symptom Occurrence and Symptom Distress Scale (MTSOSD-59R) corresponds to stool water content and how both relate to MPA usage.
METHODS
MTSOSD-59R questionnaires filled out by 700 KTRs from the TransplantLines Biobank and Cohort Study (NCT03272841) were analyzed and compared with stool water content. Stool samples (N = 345) were freeze-dried, and a water content ≥80% was considered diarrhea.
RESULTS
Self-perceived diarrhea was reported by 46%, while stool water content ≥80% was present in 23% of KTRs. MPA use was not associated with self-perceived diarrhea (odds ratio(OR) 1.32; 95% confidence interval(CI), 0.87-1.99, p = .2), while it was associated with stool water content ≥80% (OR 2.88; 95%CI, 1.41-5.89, p = .004), independent of potential confounders. Adjustment for prior MPA discontinuation because of severe diarrhea, uncovered an association between MPA use and self-perceived diarrhea (OR 1.80; 95%CI, 1.13-2.89, p = .01).
CONCLUSIONS
These results suggest that reporting bias could add to the discrepancy between both methods for diarrhea assessment. We recommend use of objective biomarkers or more extensive questionnaires which assess information on stool frequency and stool consistency, to investigate post-transplantation diarrhea.
Topics: Cohort Studies; Diarrhea; Humans; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid
PubMed: 33882147
DOI: 10.1111/ctr.14321 -
International Immunopharmacology Sep 2021Infectious complications remain a common cause of mortality after kidney transplantation (KTx). Goal of effective immunosuppressive treatment (IS) must be balanced...
INTRODUCTION
Infectious complications remain a common cause of mortality after kidney transplantation (KTx). Goal of effective immunosuppressive treatment (IS) must be balanced between decreasing incidence of acute kidney rejection (AKR) and avoiding the incidence of infections, at the same time.
MATERIALS AND METHODS
The aim of our analysis was to identify the risk of fixed daily dose (DD) of mycophenolic acid (MPA) and levels of tacrolimus (TAC) in the development of a single, recurrent infection and AKR after KTx.
RESULTS
Our analysis consisted of 100 patients after KTx (66 males, 34 females). MPA DD > 1080 mg was a risk factor (RF) for recurrent infection in general (OR 1.2964;P = 0.0277), for recurrent bacterial infection from 1 to 6 month (OR 1.2674;P = 0.0151), recurrent bacterial infection (OR 1.2574;P = 0.0436), single viral infection (OR 1.2640;P = 0.0398) from 6-12 month after KTx. MPA DD > 1080 mg and levels of TAC above recommended levels were not independent RF for the incidence of the infection.
CONCLUSION
MPA DD > 1080 mg as a RF for recurrent infection starting in the 1 month after KTx with significant association between the incidence of infections and MPA DD and TAC levels, without increased risk of AKR. In the centers with fixed dosing of IS, this can lead to lowering the risk of infections by decreasing MPA DD 1 month after KTx without increasing risk of infections.
Topics: Adult; Dose-Response Relationship, Drug; Female; Graft Rejection; Humans; Immunosuppressive Agents; Incidence; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Postoperative Complications; Reinfection; Retrospective Studies; Tacrolimus
PubMed: 34182244
DOI: 10.1016/j.intimp.2021.107908 -
Current Opinion in Gastroenterology May 2024The primary therapy of autoimmune hepatitis (AIH) has been established for over three decades. This review focuses on updates in the evaluation and management of... (Review)
Review
PURPOSE OF REVIEW
The primary therapy of autoimmune hepatitis (AIH) has been established for over three decades. This review focuses on updates in the evaluation and management of patients with AIH.
RECENT FINDINGS
The evaluation of patients has recently been updated to include more definitive screening for other autoimmune diseases, including thyroid disease and celiac disease. Antibody detection by ELISA, an easier and more commonly available method, has been incorporated into the latest iteration of the AIH scoring system. Corticosteroids and AZA remain the backbone of AIH treatment, but there is growing evidence for mycophenolate mofetil as both first-line and second-line therapy, and growing inquiry into calcineurin inhibitors. Noninvasive markers of liver disease have now been validated in AIH, with the strongest evidence for VCTE in patients with minimal hepatic inflammation.
SUMMARY
Recent research of alternative immunosuppressant therapies, noninvasive markers of fibrosis, and updated society guidelines, have improved our ability to evaluate, treat, and follow patients with AIH.
Topics: Humans; Hepatitis, Autoimmune; Immunosuppressive Agents; Mycophenolic Acid; Liver Diseases
PubMed: 38363233
DOI: 10.1097/MOG.0000000000001014 -
Frontiers in Public Health 2021Organ transplantations are difficult, complicated and very expensive interventions. In order to preserve the transplanted organs, it is necessary to provide medical...
Organ transplantations are difficult, complicated and very expensive interventions. In order to preserve the transplanted organs, it is necessary to provide medical care to the patients in terms of immunosuppression. According to the guidelines, the first-line therapy choices for achieving immunosuppression after transplantation are tacrolimus, cyclosporine, mycophenolic acid, azathioprine, sirolimus, everolimus" and corticosteroids. The aim of our study was to examine the utilization of this drugs in Montenegro and to compare the results with the ones from Finland, Croatia, and Serbia. In our investigation we used Anatomical Therapeutic Chemical/Defined Daily Dose (ATC/DDD) methodology. Prices per DDD of drugs are presented in euros (€). In all observed countries, there is a positive trend in the consumption of all 6 drugs during the analyzed period. The prices per DDD of these drugs generally show a negative trend. Tacrolimus and mycophenolic acid in Montenegro recorded the largest reduction in the price per DDD. Price per one DDD of tacrolimus decreased from €13.28 in 2009 to €5.11 in 2019, thus by about 260%, and as regards mycophenolic acid, the price per one DDD decreased from €9.59 in 2009 to € 3.36 in 2019, thus by almost 300%. Despite the reduction in the price per DDD, drugs that are used as immunosuppressants are showing increasing costs from year to year. Since these drugs are expensive, they participate in a significant percentage in the budget for medicines in each country.
Topics: Azathioprine; Croatia; Cyclosporine; Everolimus; Finland; Humans; Montenegro; Mycophenolic Acid; Serbia; Sirolimus; Tacrolimus
PubMed: 33869136
DOI: 10.3389/fpubh.2021.671316 -
GeroScience Feb 2024In genetically heterogeneous (UM-HET3) mice produced by the CByB6F1 × C3D2F1 cross, the Nrf2 activator astaxanthin (Asta) extended the median male lifespan by 12%...
Astaxanthin and meclizine extend lifespan in UM-HET3 male mice; fisetin, SG1002 (hydrogen sulfide donor), dimethyl fumarate, mycophenolic acid, and 4-phenylbutyrate do not significantly affect lifespan in either sex at the doses and schedules used.
In genetically heterogeneous (UM-HET3) mice produced by the CByB6F1 × C3D2F1 cross, the Nrf2 activator astaxanthin (Asta) extended the median male lifespan by 12% (p = 0.003, log-rank test), while meclizine (Mec), an mTORC1 inhibitor, extended the male lifespan by 8% (p = 0.03). Asta was fed at 1840 ± 520 (9) ppm and Mec at 544 ± 48 (9) ppm, stated as mean ± SE (n) of independent diet preparations. Both were started at 12 months of age. The 90th percentile lifespan for both treatments was extended in absolute value by 6% in males, but neither was significant by the Wang-Allison test. Five other new agents were also tested as follows: fisetin, SG1002 (hydrogen sulfide donor), dimethyl fumarate, mycophenolic acid, and 4-phenylbutyrate. None of these increased lifespan significantly at the dose and method of administration tested in either sex. Amounts of dimethyl fumarate in the diet averaged 35% of the target dose, which may explain the absence of lifespan effects. Body weight was not significantly affected in males by any of the test agents. Late life weights were lower in females fed Asta and Mec, but lifespan was not significantly affected in these females. The male-specific lifespan benefits from Asta and Mec may provide insights into sex-specific aspects of aging.
Topics: Female; Mice; Male; Animals; Longevity; Meclizine; Hydrogen Sulfide; Dimethyl Fumarate; Mycophenolic Acid; Phenylbutyrates; Xanthophylls; Flavonols
PubMed: 38041783
DOI: 10.1007/s11357-023-01011-0 -
Clinical Pharmacology in Drug... Nov 2022Meal timings and content related to gallbladder emptying in the enterohepatic circulation are important for explaining the high variability in mycophenolic acid...
Meal timings and content related to gallbladder emptying in the enterohepatic circulation are important for explaining the high variability in mycophenolic acid exposure. The limited sampling strategy (LSS) was established to estimate the area under the plasma concentration-time curve from time 0 to 12 hours (AUC ) of mycophenolic acid in therapeutic drug monitoring. The aim of this study is to investigate the effect of meal timings and content on the AUC of mycophenolic acid and to assess the influence of meals on LSS. A mycophenolic acid pharmacokinetic model with a mechanism-based enterohepatic circulation process was employed to perform simulations under various assumed meal scenarios. The simulations were compared to evaluate the effect of meal timings and meal content on mycophenolic acid AUC . Monte Carlo simulations were performed using the meal parameter with the greatest impact on mycophenolic acid AUC as a variable. The corresponding LSS equations were established, and the predictive performance was assessed. Both the meal timings and meal content affected the mycophenolic acid AUC , and the postdose fasting period had the greatest impact. The predictive performance of the LSS is sensitive to the postdose fasting period. Therefore, meal timings may improve the estimation of mycophenolic acid AUC and the efficacy of therapeutic drug monitoring.
Topics: Humans; Mycophenolic Acid; Area Under Curve; Immunosuppressive Agents; Drug Monitoring; Meals
PubMed: 36045559
DOI: 10.1002/cpdd.1141 -
Current Opinion in Nephrology and... May 2024As the most common primary glomerulonephritis, immunoglobulin A (IgA) nephropathy (IgAN) is an important cause of kidney failure and mortality. Until recently,... (Review)
Review
PURPOSE OF REVIEW
As the most common primary glomerulonephritis, immunoglobulin A (IgA) nephropathy (IgAN) is an important cause of kidney failure and mortality. Until recently, therapeutic options were limited. Fortunately, there have been numerous recent clinical trials demonstrating efficacy of new therapies in slowing chronic kidney disease (CKD) progression at varying stages of disease.
RECENT FINDINGS
The TESTING trial has provided high-quality evidence for slowing estimated glomerular filtration rate (eGFR) decline with a reduced-dose glucocorticoid regimen, while demonstrating an improved safety profile. Targeted-release budesonide represents a well tolerated therapy for reducing eGFR decline. Mycophenolate mofetil may reduce CKD progression in some populations, while hydroxychloroquine is efficacious in reducing proteinuria. Sodium-glucose cotransporter (SGLT2) inhibitors and sparsentan are effective therapies for CKD due to IgAN, but should not be used in lieu of disease-modifying immunosuppressive therapy. Many new therapies are approaching readiness for clinical use.
SUMMARY
Numerous therapeutic options now exist and include disease-modifying and nephroprotective drugs. Identifying the right treatment for the right patient is now the clinical challenge and, with new drugs on the horizon, represents the primary unmet research need in this rapidly-developing field.
Topics: Humans; Glomerulonephritis, IGA; Standard of Care; Renal Insufficiency, Chronic; Mycophenolic Acid; Glucocorticoids; Proteinuria
PubMed: 38411173
DOI: 10.1097/MNH.0000000000000979 -
Ocular Immunology and Inflammation Feb 2024To assess the efficacy and tolerance of hydroxychloroquine in sarcoidosis-associated uveitis.
BACKGROUND/PURPOSE
To assess the efficacy and tolerance of hydroxychloroquine in sarcoidosis-associated uveitis.
METHODS
Retrospective study on all patients with sarcoidosis-associated uveitis who were treated with hydroxychloroquine between 2003 and 2019 in a French university hospital.
RESULTS
Twenty-seven patients with sarcoidosis-associated uveitis received hydroxychloroquine. The mean duration of treatment was 20.0 ± 10.9 months. At the end of the follow-up, hydroxychloroquine success was achieved in 15 (55.6%) patients. Four of them were also on oral corticosteroids, with a prednisone dose ≤5 mg/day. Under treatment, the median prednisone dose decreased from 20.0 (interquartile range (IQR), 7-25) to 5.0 (IQR, 3-6.5) mg/day ( = .02). The incidence rate of flare decreased from 204.6 to 63.8 per 100 person-years ( = .02). Hydroxychloroquine was discontinued in 12 (44.4%) patients during follow-up, including 8 (29.6%) for ineffectiveness, and three who experienced side effects.
CONCLUSION
Hydroxychloroquine appears as an interesting option in sarcoidosis-associated uveitis. AZA: Azathioprine; BAL: Bronchoalveolar Lavage; BCVA: Best-Corrected Visual Acuity; ENT: Ears, Nose and Throat; HCQ: Hydroxychloroquine; IOP: Intra-Ocular Pressure; IQR: interquartile range; MHC: Major Histocompatibility Complex; MMF: Mycophenolate Mofetil; MTX: Methotrexate; PMSI: Programme de Médicalisation du Système d'Information; SAU: Sarcoidosis-Associated Uveitis; SD: Standard Deviation; SUN: Standard Uveitis Nomenclature.
Topics: Humans; Immunosuppressive Agents; Prednisone; Hydroxychloroquine; Retrospective Studies; Uveitis; Methotrexate; Mycophenolic Acid; Sarcoidosis; Treatment Outcome
PubMed: 36749910
DOI: 10.1080/09273948.2023.2165952 -
Clinical Gastroenterology and... Nov 2019
Topics: Aged; Esophagitis; Esophagoscopy; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid; Transplant Recipients
PubMed: 29857144
DOI: 10.1016/j.cgh.2018.05.027