Pharmacokinetics of enteric-coated mycophenolate sodium in stable liver transplant recipients

Introduction: Mycophenolate mofetil (MMF) is one of the major immunosuppressive agents used in liver transplantation recipients. In an attempt to mitigate one of the most common side effects of MMF (gastrointestinal symptoms), enteric-coated mycophenolate sodium (EC-MPS) was developed. In this study, we report the pharmacokinetic profile of EC-MPS in stable liver transplantation recipients administered a single 720 mg dose. Methods: Liver transplantation recipients more than one yr after transplantation were administered a single dose of 720 mg EC-MPS after which blood levels of MPA were measured at frequent intervals using a specific and validated LC-MS/MS assay. Results: The characteristics of the 21 patients studied were: mean age was 55.9 yr, 13 were female, eight had hepatitis C, and 14 were on tacrolimus. The mean apparent half-life of MPA was 5.3 +/- 4.3 h, (1.0-15.7). Mean t(max) was 2.4 +/- 1.1 h (1.0-5.0). The mean area-under-curve was 45.3 +/- 23.1 mu g-h/mL (17.3-90.0). Trough level concentrations (C-12 h) showed large inter-individual variability (0-9.2 mu g/mL). There was no difference in any of the pharmacokinetic parameters relative to: gender, HCV, administration of tacrolimus vs. cyclosporine or type of biliary anastomosis. Conclusions: There is a wide variation in pharmacokinetic parameters in stable, long-term liver transplantation recipients receiving a single dose of EC-MPS. These data suggest that therapeutic drug monitoring with EC-MPS may have limited utility in liver transplantation recipients.