title: Enteric-coated mycophenolate sodium delivers bioequivalent MPA exposure compared with mycophenolate mofetil.
abstract: 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-infinity)) compared with 1000 mg MMF: 60.7 microg h/mL for 640 mg EC-MPS, 66.5 microg h/mL for 720 mg EC-MPS, and 63.7 microg 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.
authors.affiliation: Merheim Medical Center, Cologne General Hospital, Cologne, Germany. wolfgang.arns@uni-koeln.de
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Arns
authors.forename: Stephan
authors.initials: S
authors.lastname: Breuer
authors.forename: Somesh
authors.initials: S
authors.lastname: Choudhury
authors.forename: Guy
authors.initials: G
authors.lastname: Taccard
authors.forename: James
authors.initials: J
authors.lastname: Lee
authors.forename: Vera
authors.initials: V
authors.lastname: Binder
authors.forename: Jürgen
authors.initials: J
authors.lastname: Roettele
authors.forename: Robert
authors.initials: R
authors.lastname: Schmouder
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D016572:Cyclosporine / Q000627:therapeutic use; D016503:Drug Delivery Systems; D005260:Female; D005965:Glucuronates / Q000008:administration & dosage / Q000493:pharmacokinetics; D020719:Glucuronides; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D012449:Safety; D012995:Solubility; D013608:Tablets, Enteric-Coated; D013810:Therapeutic Equivalency
chemical_list: D005965:Glucuronates; D020719:Glucuronides; D007166:Immunosuppressive Agents; D013608:Tablets, Enteric-Coated; C113145:mycophenolic acid glucuronide; D016572:Cyclosporine; D009173:Mycophenolic Acid