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 C_12h were correlated (r = 0.78, p = 0.0001), but EC-MPS–MPA C_max 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 m², 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.