Therapeutic drug monitoring of mycophenolate mofetil and enteric-coated mycophenolate sodium in patients with systemic lupus erythematosus

Objective: Mycophenolic acid (MPA), the active form of mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), is used to treat systemic lupus erythematosus (SLE). MMF and EC-MPS pharmacokinetics were examined to devise guidance for therapeutic drug monitoring (TDM) for SLE patients with normal renal function. Research design and methods: This observational study included 21 patients receiving MMF (1000 mg twice daily) and 14 taking EC-MPS (720 mg twice daily). MPA AUC between 0 and 12 h (AUC(0-) (12h)), C-max, T-max, and 12-h trough concentrations (C-12h) were determined. Results: Means of dose-normalized MMF- or EC-MPS-MPA C-max were 64.6 +/- 25 and 61.4 +/- 27.1 h mg/l, respectively. MPA T-max for EC-MPS was longer and more variable than for MMF. MMF-MPA AUC(0-) (12h) and C12h were correlated (r = 0.78, p = 0.0001), but EC-MPS-MPA Cmax and single concentrations were weakly correlated. A limited-sampling strategy (LSS) combining C-max and C-12h gave satisfactory predictive performance to estimate MPA AUC(0-) (12h) after EC-MPS administration. Conclusions: For TDM in SLE patients with GFR > 60 ml/min/1.73 m(2), C-12h after MMF ingestion could predict MPA AUC(0-) (12h), while an LSS around T-max should be used for patients on EC-MPS.