mycophenolic-acid-glucuronide and Renal-Insufficiency

mycophenolic-acid-glucuronide has been researched along with Renal-Insufficiency* in 3 studies

Trials

2 trial(s) available for mycophenolic-acid-glucuronide and Renal-Insufficiency

ArticleYear
Mycophenolic acid pharmacokinetics during maintenance immunosuppression in African American and Caucasian renal transplant recipients.
    Journal of clinical pharmacology, 2011, Volume: 51, Issue:8

    Renal transplant recipients exhibit variability in mycophenolic acid (MPA) and MPA glucuronide (MPAG) pharmacokinetics, which are influenced by clinical and demographic factors. Racial influence on MPA and MPAG pharmacokinetics was investigated in 53 patients: 17 African American males, 22 Caucasian males, and 14 females receiving mycophenolate mofetil (MMF) and cyclosporine. A 12-hour steady-state pharmacokinetic study was conducted. Enterohepatic circulation of MPA was characterized by a second plasma concentration peak and was included in a novel statistical model with MPAG. MPA clearance in African American males was 26.5 ± 14.4 L/h versus 17.9 ± 6.1 L/h in Caucasian males (P = .035) and 16.1 ± 4.6 L/h in Caucasian females (P = .024) with no difference noted in MPA troughs. Enterohepatic circulation occurred less frequently in African American males (23%) compared with Caucasian males (42%) and Caucasian females (50%) (P > .05). Cyclosporine exposure was correlated with MPA and MPAG pharmacokinetics, whereas creatinine clearance influenced MPAG pharmacokinetics. A racial difference was noted with more rapid MPA clearance in African American males compared with Caucasians. The results support differential MPA dosing and the role of therapeutic drug monitoring in addition to considering the influence of renal function and concurrent immunosuppressives on MPA and MPAG pharmacokinetics.

    Topics: Adult; Aged; Black or African American; Cyclosporine; Drug Therapy, Combination; Enterohepatic Circulation; Female; Glucuronides; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Metabolic Clearance Rate; Middle Aged; Models, Biological; Mycophenolic Acid; Prodrugs; Renal Insufficiency; White People

2011
Influence of clinical and demographic variables on mycophenolic acid pharmacokinetics in antineutrophil cytoplasmic antibody-associated vasculitis.
    The Annals of pharmacotherapy, 2009, Volume: 43, Issue:6

    Mycophenolic acid (MPA) is used off-label to treat many forms of glomerulonephritis.. To evaluate the pharmacokinetics of MPA and its glucuronide (MPAG) in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis patients with renal manifestations and to determine the effects of clinical (urinary protein excretion, serum albumin, creatinine clearance) and demographic (age, race, sex) variables on MPA and MPAG pharmacokinetics.. Twenty-three patients taking MPA at steady-state were evaluated. Plasma and urine samples were collected over 24 hours. Analyses included noncompartmental pharmacokinetics and statistics including Mann-Whitney U test and univariate/multiple regression.. MPA clearance (Cl/F 288 +/- 154 mL/min) was approximately 2-fold higher than previously reported from transplant patients and predicted by weight and race (ranked MPA Cl/F = -11.766 + 0.2035 [wt] + 4.9578 [race]; R(2) 41.8%; p = 0.005). Creatinine clearance (CrCl) less than 60 mL/min resulted in higher MPA exposure, total area under the curve (AUC)(0-12), and AUC(6-12), as well as unbound AUC(0-12). The metabolic ratio (MPAG(AUC)/MPA(AUC)) of 8.67 +/- 5.57 was lower than that previously reported in renal transplant recipients.. Diminished kidney function (eg, CrCl <60 mL/min) demonstrated enhanced MPA and MPAG exposure in patients with ANCA vasculitis. However, unlike renal transplant recipients, patients with ANCA vasculitis had enhanced Cl/F and diminished metabolic ratio, suggesting the need to comprehensively evaluate the role of disease-specific factors on MPA pharmacokinetics.

    Topics: Adult; Aged; Antibodies, Antineutrophil Cytoplasmic; Area Under Curve; Enzyme Inhibitors; Female; Glucuronides; Humans; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Regression Analysis; Renal Insufficiency; Statistics, Nonparametric; Vasculitis

2009

Other Studies

1 other study(ies) available for mycophenolic-acid-glucuronide and Renal-Insufficiency

ArticleYear
Influence of renal insufficiency on pharmacokinetics of ACYL-glucuronide metabolite of mycophenolic acid in renal transplant patients.
    Transplantation proceedings, 2007, Volume: 39, Issue:7

    The acyl glucuronide of mycophenolic acid (AcMPAG) is a metabolite with in vitro immunosuppressive activity. The chemical properties of acyl glucuronides have been associated with the toxicity of some drugs. The aim of our study was to analyze the influence of renal insufficiency on the pharmacokinetics of AcMPAG. Areas under the 12-hour curve (AUC(0-12h)) of MPA, glucuronide of MPA (MPAG), and AcMPAG were determined by high performance liquid chromatography performed in 20 renal transplantation patients under treatment with mycophenolate mofetil (MMF), cyclosporine, and steroids. They were divided between a group with preserved renal function (group I, mean creatinine clearance [Clcr] of 105 +/- 7 mL/min) and one with advanced renal insufficiency (group II, mean Clcr of 27 +/- 5 mL/min). There was no difference in MMF dose or MPA-AUC(0-12h) values between groups. Mean predose levels of AcMPAG-C0 and AcMPAG-AUC(0-12h) were much higher in group II than in group I (0.5 +/- 2 vs 1.6 +/- 1 microg/mL and 12 +/- 2 vs. 32 +/- 19 microg*h/mL respectively, P < .005). The present data suggested that AcMPAG, a metabolite with immunosuppressive activity that may be related to toxic effects of MPA, is renally eliminated. Its levels can significantly rise in patients with renal insufficiency. Although further studies with more patients are required to determine the role of AcMPAG in MPA toxicity, we believe that this accumulation may be of clinical relevance.

    Topics: Adult; Chromatography, High Pressure Liquid; Female; Glucuronides; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Renal Insufficiency

2007