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Enteric‐coated mycophenolate sodium delivers bioequivalent MPA exposure compared with mycophenolate mofetil
Author(s) -
Arns Wolfgang,
Breuer Stephan,
Choudhury Somesh,
Taccard Guy,
Lee James,
Binder Vera,
Roettele Jürgen,
Schmouder Robert
Publication year - 2005
Publication title -
clinical transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 76
eISSN - 1399-0012
pISSN - 0902-0063
DOI - 10.1111/j.1399-0012.2004.00318.x
Subject(s) - bioequivalence , mycophenolic acid , medicine , mycophenolate , enteric coating , pharmacology , pharmacokinetics , bioavailability , transplantation , crossover study , adverse effect , urology , gastroenterology , dosage form , alternative medicine , pathology , placebo
Mycophenolic acid (MPA), the active moiety of mycophenolate mofetil (MMF), is routinely used as an adjunct immunosuppressant therapy in renal transplantation. Although highly effective, MMF therapy is associated with significant gastrointestinal adverse effects. Enteric‐coated mycophenolate sodium (EC‐MPS) is an advanced formulation delivering MPA. The enteric coat dissolves at pH > 5 allowing for MPA delivery in the small intestine. A single‐center, open‐label, randomized, three‐way crossover study of 24 stable Caucasian renal transplant patients receiving cyclosporine‐based immunosuppression, compared the relative bioavailability of two EC‐MPS doses (640 and 720 mg) with MMF (1000 mg). Both EC‐MPS doses delivered bioequivalent mean MPA exposure ( AUC 0−∞ ) compared with 1000 mg MMF: 60.7 μ g h/mL for 640 mg EC‐MPS, 66.5 μ g h/mL for 720 mg EC‐MPS, and 63.7 μ g h/mL for 1000 mg MMF. Median t max was significantly delayed for both EC‐MPS doses compared with MMF (2.0 h vs. 0.75 h, respectively; p < 0.01), consistent with a functional enteric coating of EC‐MPS. Furthermore, both EC‐MPS doses were bioequivalent to 1000 mg MMF for AUC and C max for mycophenolic acid glucuronide. All three treatments were well tolerated. The EC‐MPS 720 mg dose most closely approximated the MPA exposure of 1000 mg MMF and was selected for subsequent phase III studies.