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Omeprazole Impairs the Absorption of Mycophenolate Mofetil But Not of Enteric‐Coated Mycophenolate Sodium in Healthy Volunteers
Author(s) -
Kees M. G.,
Steinke T.,
Moritz S.,
Rupprecht K.,
Paulus E. M.,
Kees F.,
Bucher M.,
Faerber L.
Publication year - 2012
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270011412968
Subject(s) - mycophenolic acid , mycophenolate , chemistry , omeprazole , pharmacokinetics , bioavailability , pharmacology , glucuronide , antacid , enteric coating , oral administration , chromatography , crossover study , metabolite , dosage form , transplantation , medicine , biochemistry , alternative medicine , pathology , placebo
In 2 crossover studies, 12 healthy volunteers (6 male/6 female) received a single oral dose of mycophenolate mofetil (MMF) 1000 mg or an equimolar dose of enteric‐coated mycophenolate sodium (EC‐MPS) 720 mg fasting with and without coadministered omeprazole 20 mg bid. The plasma concentrations of mycophenolic acid (MPA) and of the inactive metabolite mycophenolic acid glucuronide (MPA‐G) were measured by high‐performance liquid chromatography (HPLC). In addition, dissolution of MMF 500 mg or EC‐MPS 360 mg tablets was determined using an USP paddle apparatus in aqueous buffer of pH 1 to 7. The bioavailability of MPA following administration of MMF or EC‐MPS was similar except for the time to peak concentration, which was longer in the EC‐MPS group. Concomitant treatment with omeprazole lowered significantly C max and AUC 12h of MPA following administration of MMF. The pharmacokinetics of EC‐MPS was not affected. Dissolution of MMF in aqueous buffer decreased dramatically at pH above 4.5. The EC‐MPS tablet was stable up to pH 5. Above, EC‐MPS was quantitatively disintegrated and MPS quantitatively dissolved. There is strong evidence that impaired absorption of MMF with concomitant proton pump inhibitors is due to incomplete dissolution of MMF in the stomach at elevated pH.