The proton pump inhibitor pantoprazole and its interaction with enteric-coated mycophenolate sodium in transplant recipients.
BACKGROUND
In this prospective study we investigated the impact of the proton pump inhibitor (PPI) pantoprazole on the bioavailability of mycophenolic acid (MPA) after oral administration of enteric-coated mycophenolate sodium (EC-MPS; Myfortic) in heart or lung transplant recipients. Previously we demonstrated that pantoprazole reduces the MPA exposure of mycophenolate mofetil (MMF; CellCept) by 34% in area under the concentration-time curve (AUC). Because gastrointestinal side-effects are common after organ transplantation, we investigated the effect of PPI on MPA levels in patients receiving EC-MPS.


METHODS
MPA plasma concentrations and inosine monophosphate dehydrogenase (IMPDH) activity at baseline, 30 minutes and 1, 2, 3 and 4 hours were obtained from 21 patients. These patients were treated with pantoprazole 40 mg once daily and EC-MPS twice daily at a mean dose of 960 mg. Measurements were repeated after pantoprazole withdrawal.


RESULTS
MPA concentrations and IMPDH activities did not reveal any significant difference during PPI treatment and after withdrawal. MPA AUC, MPA C(max) (maximal MPA concentration), the time until C(max) was reached (T(max)) and IMPDH activity AUC all showed no significant difference.


CONCLUSIONS
We did not find an influence of pantoprazole on EC-MPS pharmacokinetics such as we did for MMF in our previous investigation. A further prospective, large, cross-over study is planned to support these preliminary results. Given that MPA exposure by AUC correlates with the incidence of acute rejection episodes and transplant vasculopathy, the present findings may have clinical implications.
Department of Cardiology, Ludwig Maximilians University Munich, Munich, Germany. sieglinde.kofler@med.uni-muenchen.de
Sieglinde
S
Kofler
Christine
C
Wolf
Natalija
N
Shvets
Zeljka
Z
Sisic
Thomas
T
Müller
Jürgen
J
Behr
Hae-Young
HY
Sohn
Michael
M
Vogeser
Maria
M
Shipkova
Bruno
B
Meiser
Gerhard
G
Steinbeck
Bruno
B
Reichart
Ingo
I
Kaczmarek
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000627:therapeutic use*; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D004347:Drug Interactions; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000378:metabolism / Q000517:prevention & control*; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007168:IMP Dehydrogenase / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016040:Lung Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D000077402:Pantoprazole; D011446:Prospective Studies; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D012189:Retrospective Studies; D013608:Tablets, Enteric-Coated
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D007166:Immunosuppressive Agents; D054328:Proton Pump Inhibitors; D013608:Tablets, Enteric-Coated; D000077402:Pantoprazole; D007168:IMP Dehydrogenase; C488211:IMPDH1 protein, human; D009173:Mycophenolic Acid