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

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  • Mino Yasuaki
    Department of Hospital Pharmacy, Hamamatsu University School of Medicine
  • Naito Takafumi
    Department of Hospital Pharmacy, Hamamatsu University School of Medicine
  • Shimoyama Kumiko
    Third Department of Internal Medicine, Hamamatsu University School of Medicine
  • Ogawa Noriyoshi
    Third Department of Internal Medicine, Hamamatsu University School of Medicine
  • Kawakami Junichi
    Department of Hospital Pharmacy, Hamamatsu University School of Medicine

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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.

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