title: Pharmacokinetic variability of mycophenolic acid and its glucuronide in systemic lupus erythematosus patients in remission maintenance phase.
abstract: 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 (C₀) of MPA (adjusted R²=0.305, p=0.01) in a multivariate analysis. Dose-normalized MPAG C₀ was significantly correlated with only creatinine clearance (adjusted R²=0.135, p=0.03). The free fraction of MPA was significantly correlated with only serum albumin (adjusted R²=0.700, p<0.01). The free fraction of MPAG was significantly correlated with serum albumin, metal medication, and age (adjusted R²=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.
authors.affiliation: Department of Hospital Pharmacy, Hamamatsu University School of Medicine, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Mino
authors.forename: Takafumi
authors.initials: T
authors.lastname: Naito
authors.forename: Kumiko
authors.initials: K
authors.lastname: Shimoyama
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Ogawa
authors.forename: Junichi
authors.initials: J
authors.lastname: Kawakami
mesh_terms: D000328:Adult; D003404:Creatinine / Q000652:urine; D005260:Female; D020719:Glucuronides / Q000737:chemistry*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D020719:Glucuronides; D003404:Creatinine; D009173:Mycophenolic Acid