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 (AUC012h), C_max, T_max, and 12-h trough concentrations (C12h) were determined. Results: Means of dose-normalized MMF or EC-MPSMPA 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 AUC012h and C12h were correlated (r 0.78, p 0.0001), but EC-MPSMPA C _max and single concentrations were weakly correlated. A limited-sampling strategy (LSS) combining Cmax and C12h gave satisfactory predictive performance to estimate MPA AUC012h after EC-MPS administration. Conclusions: For TDM in SLE patients with GFR >60 ml/min/1.73 m², C12h after MMF ingestion could predict MPA AUC012h, while an LSS around T _max should be used for patients on EC-MPS.