mycophenolic-acid-glucuronide and Body-Weight

Previous studies have shown poor absorption of enteric-coated mycophenolate sodium (E-MPS) during the initial post-kidney transplantation (KT) period. The percentage of patients with adequate therapeutic exposure (target AUC 30-60 microg.h/mL) of mycophenolic acid is 55%, 86%, and 100% at days 14, 90, and 180 postgrafting. To assess the adequacy of mycophenolic acid (MPA) delivery during the initial period, we prospectively studied the pharmacokinetics (AUC0-12 h of MPA (measured by high-performance liquid chromatography) in 12 patients after their first single dose of 720 mg of oral E-MPS and 3 to 8 months after 720 mg twice a day prescribed daily. Concomitant immunosuppression included CsA and prednisolone. Evaluation of the pharmacokinetic profiles was repeated at 2 weeks. The patients' mean +/- SD body weight was 48.1 +/- 8.8 kg; their mean (range) values of AUC0-12 h for MPA were 73.9 +/- 49.5 microg.h/ml (31.9-190) on day 1 and 74.3 +/- 44.3 (30.5-178) microg.h/ml on day 14. The mean nadir serum creatinine was 1.1 +/- 0.4 mg/dL. The patient and graft survival rates were 100%. Two patients (15%) developed significant diarrhea requiring E-MPS dose reduction. Other complications included urinary tract infections (n = 2), CMV syndrome (n = 1), borderline acute rejection (n = 1), and reversible CsA nephrotoxicity (n = 3). We conclude that the use of a standard dose of E-MPS results in immediate delivery of adequate therapeutic systemic MPA exposure in all patients. The absorption profile was better than that described previously.

Topics: Administration, Oral; Adult; Body Weight; Drug Monitoring; Glucuronates; Glucuronides; Humans; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid; Tablets, Enteric-Coated

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