mycophenolic-acid-glucuronide has been researched along with Lupus-Erythematosus--Systemic* in 4 studies
1 review(s) available for mycophenolic-acid-glucuronide and Lupus-Erythematosus--Systemic
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[Optimization of Immunosuppression and the Prevention of Fungal Infection in Autoimmune Diseases].
Mycophenolate mofetil (MMF) has recently been reported to be effective in the treatment of systemic lupus erythematosus (SLE). The therapeutic range of mycophenolic acid (MPA) and its 7-O-glucuronide (MPAG), and factors affecting their pharmacokinetics, remain to be clarified. The influence of the pharmacokinetics of MPA and MPAG on the activity of inosine 5'-monophosphate dehydrogenase (IMPDH), a target of the MPA, also remains to be revealed. The pharmacokinetic variability of hydroxy-itraconazole (OH-ITZ), an active metabolite of itraconazole frequently co-administered with immunosuppressants in immunocompromised patients, is not fully known. The aim of this study was to establish the optimal dosage and administration of immunosuppressants and antifungal agents. MMF improved clinical laboratory markers and reduced prednisolone dosage in 31 SLE patients, with a pre-dose plasma concentration of MPA and MPAG in the interquartile ranges of 0.94-2.96 and 18.6-53.7 μg/mL, respectively. Renal function and co-administered metal influenced the pharmacokinetics of MPA and MPAG in 31 SLE patients in the remission maintenance phase. IMPDH activity was induced in 29 SLE patients receiving the MMF therapy. This induction was dependent on the plasma concentration of MPAG, but not MPA. In addition, IMPDH activity was negatively correlated with complement fraction C3. MPA exposure and disease activity in SLE patients may determine IMPDH activity. The pharmacokinetic variability of OH-ITZ was associated with saturated metabolism to keto-itraconazole, serum concentration of albumin, and renal function in 46 immunocompromised patients. Prevention of fungal infections and drug-drug interactions in immunocompromised patients can be obtained by considering these identified confounding factors. Topics: Complement C3; Drug Interactions; Drug Monitoring; Drug Therapy, Combination; Glucuronides; Humans; Immunocompromised Host; Immunosuppressive Agents; IMP Dehydrogenase; Individuality; Itraconazole; Lupus Erythematosus, Systemic; Mycophenolic Acid; Mycoses; Prednisolone | 2015 |
1 trial(s) available for mycophenolic-acid-glucuronide and Lupus-Erythematosus--Systemic
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Effective plasma concentrations of mycophenolic acid and its glucuronide in systemic lupus erythematosus patients in the remission-maintenance phase.
Mycophenolate mofetil (MMF) has been reported recently to be effective in the treatment of systemic lupus erythematosus (SLE). The therapeutic range of mycophenolic acid (MPA) in SLE in the remission-maintenance phase remains to be clarified. The aim of this study was to evaluate the therapeutic efficacy of MMF and predose plasma concentrations of MPA and its phenolic glucuronide (MPAG) in patients with SLE in the remission-maintenance phase.. Thirty-one patients with SLE receiving a fixed dosage regimen of MMF (median and interquartile range, 1500 and 1000-2000mg/day) for at least 1month and who had not experienced any adverse drug reactions for more than 3months were enrolled.. Significant improvement was observed after MMF administration in total haemolytic complement CH(50) and its fractions C3 and C4, immunoglobulins IgG, IgA and IgM, anti-dsDNA antibody, serum concentration of albumin and red blood cell count, even though the mean daily dose of prednisolone was significantly reduced (P=0·02). Median predose plasma concentrations of MPA and MPAG were 1·95 and 26·2μg/mL (interquartile ranges, 0·94-2·96 and 18·6-53·7 μg/mL). Predose plasma concentrations of MPA and MPAG correlated significantly with MMF dose (r=0·64, P<0·01 and r=0·39, P=0·03).. MMF improved clinical laboratory markers and reduced prednisolone dosage in SLE patients with predose plasma concentration of MPA and MPAG in the interquartile ranges of 0·94-2·96 and 18·6-53·7μg/mL, respectively. Topics: Adult; Dose-Response Relationship, Drug; Female; Glucocorticoids; Glucuronides; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Male; Middle Aged; Mycophenolic Acid; Prednisolone; Treatment Outcome | 2012 |
2 other study(ies) available for mycophenolic-acid-glucuronide and Lupus-Erythematosus--Systemic
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Mycophenolic acid exposure and complement fraction C3 influence inosine 5'-monophosphate dehydrogenase activity in systemic lupus erythematosus.
Background Mycophenolate mofetil has recently been reported to be effective against systemic lupus erythematosus. The influence of the pharmacokinetics of mycophenolic acid, the active form of mycophenolate mofetil and the major inactive mycophenolic acid phenolic glucuronide on the activity of the target enzyme inosine 5'-monophosphate dehydrogenase, is expected to be revealed. The aim of this study was to identify the factors associated with inosine 5'-monophosphate dehydrogenase activity in systemic lupus erythematosus patients. Methods Fifty systemic lupus erythematosus patients in remission maintenance phase (29 received mycophenolate mofetil [MMF+] and 21 did not [MMF-]) were enrolled. Median and interquartile range of dose of mycophenolate mofetil were 1500 and 1000-1500 mg/day, respectively. Stepwise multiple linear regression analysis was performed to assess the dependence between inosine 5'-monophosphate dehydrogenase activity and 25 predictor values including predose plasma concentrations of free mycophenolic acid and mycophenolic acid phenolic glucuronide. Results Median and interquartile range of predose total plasma concentrations of mycophenolic acid and mycophenolic acid phenolic glucuronide were 2.73 and 1.43-5.73 and 25.5 and 13.1-54.7 µg/mL, respectively. Predose inosine 5'-monophosphate dehydrogenase activity was significantly higher in MMF+ than MMF- patients (median 38.3 and 20.6 nmoL xanthosine 5'-monophosphate/g haemoglobin/h, P<0.01). The plasma concentration of free mycophenolic acid phenolic glucuronide, complement fraction C3 and body weight were significant predictors accounting for interindividual variability in the inosine 5'-monophosphate dehydrogenase activity (adjusted R Topics: Adult; Body Weight; Complement C3; Cross-Sectional Studies; Drug Administration Schedule; Female; Glucuronides; Humans; Immunosuppressive Agents; IMP Dehydrogenase; Lupus Erythematosus, Systemic; Male; Middle Aged; Multivariate Analysis; Mycophenolic Acid; Remission Induction; Ribonucleotides; Xanthine | 2017 |
Development of population PK model with enterohepatic circulation for mycophenolic acid in patients with childhood-onset systemic lupus erythematosus.
This study aimed to develop a population pharmacokinetic (PK) enterohepatic recycling model for MPA in patients with childhood-onset systemic lupus erythematosus (cSLE).. MPA concentration-time data were from outpatients on stable oral mycophenolate mofetil (MMF) and collected under fasting conditions, with standardized meals (1 and 4 h post-dose). Sampling times were pre-dose, 20, 40 min, 1, 1.5, 2, 3, 4, 6 and 9 h, post dose. The population PK analysis simultaneously modelled MPA and 7-O-MPA-β-glucuronide (MPAG) concentrations using nonlinear mixed effect modelling.. PK analysis included 186 MPA and MPAG concentrations (mg l(-1)) from 19 patients. cSLE patients, age range 10-28 years, median 16.5 years were included. Mean ± SD disease duration was 3.8 ± 3.7 years. The final PK model included a gallbladder compartment for enterohepatic recycling and bile release time related to meal times, with first order absorption and single series of transit compartments. The PK estimates for MPA were CL(1) /F 25.3 l h(-1), V(3) /F 20.9 l, V(4) /F 234 l and CL(2) /F 19.8 l h(-1).. The final model fitted the complex processes of absorption and enterohepatic circulation (EHC) in those treated with MMF for cSLE and could be applied in Bayesian dose optimization algorithms. Topics: Administration, Oral; Adolescent; Adult; Bayes Theorem; Child; Enterohepatic Circulation; Enzyme Inhibitors; Female; Glucuronides; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Male; Models, Biological; Mycophenolic Acid; Young Adult | 2012 |