Bioavailability of mycophenolate mofetil and enteric-coated mycophenolate sodium is differentially affected by pantoprazole in healthy volunteers.
The influence of pantoprazole 40 mg twice daily on the bioavailability of a single dose of mycophenolate mofetil 1000 mg or enteric-coated mycophenolate sodium is investigated in healthy volunteers. The plasma concentrations of mycophenolic acid and of the inactive metabolite mycophenolic acid glucuronide are measured by high-performance liquid chromatography. The pharmacokinetic parameters following sole administration are similar for mycophenolate mofetil and enteric-coated mycophenolate sodium except for the time to peak concentration, which is longer in the enteric-coated mycophenolate sodium group. Concomitant treatment with pantoprazole significantly (P < .001) lowers the mycophenolic acid exposure following administration of mycophenolate mofetil. The peak concentrations drop by 57%, and area under the curve decreases from 0 to 12 hours by 27%. In contrast, pantoprazole does not change the pharmacokinetics of enteric-coated mycophenolate sodium. Given that mycophenolic acid exposure correlates with the incidence of biopsy-proven acute rejections in renal transplant recipients, these findings may have clinical implications. Administration of pantoprazole in combination with mycophenolate mofetil could possibly result in an insufficient mycophenolic acid exposure, increasing the risk of treatment failure.
Department of Anesthesiology, University of Regensburg, Regensburg, Germany.
Korbinian
K
Rupprecht
Christoph
C
Schmidt
Anne
A
Raspé
Frank
F
Schweda
Maria
M
Shipkova
Wolfgang
W
Fischer
Michael
M
Bucher
Frieder
F
Kees
Lothar
L
Faerber
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000009:adverse effects* / Q000097:blood; D000897:Anti-Ulcer Agents / Q000009:adverse effects; D001682:Biological Availability; D004347:Drug Interactions; D005260:Female; D020719:Glucuronides / Q000097:blood; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000077402:Pantoprazole; D013608:Tablets, Enteric-Coated / Q000493:pharmacokinetics; D013997:Time Factors
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D020719:Glucuronides; D007166:Immunosuppressive Agents; D013608:Tablets, Enteric-Coated; C113145:mycophenolic acid glucuronide; D000077402:Pantoprazole; D009173:Mycophenolic Acid