The proton pump inhibitor pantoprazole and its interaction with enteric-coated mycophenolate sodium in transplant recipients

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• 作者：Sieglinde Kofler MD^a ; ^{sieglinde.kofler@med.uni-muenchen.de} ; Christine Wolf MD^a ; Natalija Shvets MD^a ; Zeljka Sisic^a ; Thomas Mü ; ller MD^b ; Jü ; rgen Behr MD^a ; Hae-Young Sohn MD^c ; Michael Vogeser MD^d ; Maria Shipkova MD^e ; Bruno Meiser MD^f ; Gerhard Steinbeck MD^a ; Bruno Reichart MD^f ; Ingo Kaczmarek MD^f
• 关键词：mycophenolic acid ; enteric-coated mycophenolate sodium ; pantoprazole ; organ transplantation ; pharmacokinetics ; drug interaction ; gastrointestinal intolerance
• 刊名：The Journal of Heart and Lung Transplantation
• 出版年：2011
• 出版时间：May 2011
• 年：2011
• 卷：30
• 期：5
• 页码：565-571
• 全文大小：253 K

文摘

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.

Conclusion

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.