Pharmacokinetic Analysis of Mycophenolate Mofetil and Enteric-Coated Mycophenolate Sodium in Calcineurin Inhibitor-Free Renal Transplant Recipients

Background:Considerable interest exists in identifying calcineurin inhibitor (CNI)-free and thus, less-toxic immunosuppressive regimens, with mycophenolic acid (MPA)-based treatments being a suitable approach. Because pharmacokinetic analyses of MPA treatments in stable CNI-free renal transplant recipients are lacking, the authors aimed at comparing the steady-state pharmacokinetic characteristics of MPA in patients on stable treatment with mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS) plus prednisone (5 mg/d).Methods:In the prospective, nonrandomized, open-label study, patients with stable transplant function since 6 months received their routine single dose of either MMF (n = 12) or EC-MPS (n = 11). The MPA plasma concentration was recorded over 12 hours. Parameters assessed were predose MPA concentration (C-0), postdose minimum and maximum concentration (C-min and C-max), time to maximum concentration (T-max), and area under the concentration-time curve (AUC) for the 12-hours of exposure (AUC(0-12)).Results:Baseline characteristics were comparable between both the groups. Consistent with enteric coating, the mean T-max was significantly longer after the intake of EC-MPS compared with MMF (2.2 versus 0.8 hours; P = 0.0002). The exposure measures C-min, C-max, and AUC(0-12) were not significantly different despite the higher mean MPA equivalent dose in patients receiving MMF compared with those receiving EC-MPS (85% versus 64% of the recommended single dose, respectively). Exposures as reflected by the median AUC(0-12) values were 50.7 and 58.7 mgh(-1)L(-1) with MMF and EC-MPS, respectively (P = 0.340). All patients achieved a target AUC of >30 mgh(-1)L(-1), and 61% had an AUC of >50 mgh(-1)L(-1).Conclusions:The study provides first results on the steady-state pharmacokinetics of the 2 MPA drugs in CNI-free immunosuppressant regimens. Pharmacokinetic parameters measured in this study under real-life conditions were comparable in patients receiving MMF or EC-MPS.