Pharmacokinetic Variability of Mycophenolic Acid and Its Glucuronide in Systemic Lupus Erythematosus Patients in Remission Maintenance Phase

The aim of this study was to identify factors affecting the pharmacokinetics of mycophenolic acid (MPA) and its 7-O-glucuronide (MPAG) in systemic lupus erythematosus (SLE) patients. Thirty-one SLE patients in remission maintenance phase treated with mycophenolate mofetil (median 1500 mg/d) and prednisolone and followed-up for up to 56 months (median 13 months) were enrolled. Creatinine clearance and metal medication were significant predictors accounting for interindividual variability in the dose-normalized predose plasma concentration (C-0) of MPA (adjusted R-2=0.305, p=0.01) in a multivariate analysis. Dose-normalized MPAG C-0 was significantly correlated with only creatinine clearance (adjusted R-2=0.135, p=0.03). The free fraction of MPA was significantly correlated with only serum albumin (adjusted R-2=0.700, p<0.01). The free fraction of MPAG was significantly correlated with serum albumin, metal medication, and age (adjusted R-2=0.598, p=0.02). In conclusion, renal function and co-administered metal influenced the pharmacokinetics of MPA and MPAG in SLE patients in remission maintenance phase.