Drug Safety

, Volume 29, Issue 9, pp 769–784 | Cite as

Pharmacokinetic Drug Interaction Profiles of Proton Pump Inhibitors

  • Henning BlumeEmail author
  • Frank Donath
  • André Warnke
  • Barbara S. Schug
Review Article


Proton pump inhibitors are used extensively for the treatment of gastric acid-related disorders because they produce a greater degree and longer duration of gastric acid suppression and, thus, better healing rates, than histamine H2 receptor antagonists. The need for long-term treatment of these disorders raises the potential for clinically significant drug interactions in patients receiving proton pump inhibitors and other medications. Therefore, it is important to understand the mechanisms for drug interactions in this setting. Proton pump inhibitors can modify the intragastric release of other drugs from their dosage forms by elevating pH (e.g. reducing the antifungal activity of ketoconazole). Proton pump inhibitors also influence drug absorption and metabolism by interacting with adenosine triphosphate-dependent P-glycoprotein (e.g. inhibiting digoxin efflux) or with the cytochrome P450 (CYP) enzyme system (e.g. decreasing simvastatin metabolism), thereby affecting both intestinal first-pass metabolism and hepatic clearance.

Although interactions based on the change of gastric pH are a group-specific effect and thus may occur with all proton pump inhibitors, individual proton pump inhibitors differ in their propensities to interact with other drugs and the extent to which their interaction profiles have been defined. The interaction profiles of omeprazole and pantoprazole have been studied most extensively. A number of studies have shown that omeprazole carries a considerable potential for drug interactions, since it has a high affinity for CYP2C19 and a somewhat lower affinity for CYP3A4. In contrast, pantoprazole appears to have lower potential for interactions with other medications. Although the interaction profiles of esomeprazole, lansoprazole and rabeprazole have been less extensively investigated, evidence suggests that lansoprazole and rabeprazole seem to have a weaker potential for interactions than omeprazole.

Although only a few drug interactions involving proton pump inhibitors have been shown to be of clinical significance, the potential for drug interactions should be taken into account when choosing a therapy for gastric acid-related disorders, especially for elderly patients in whom polypharmacy is common, or in those receiving a concomitant medication with a narrow therapeutic index.


Omeprazole Proton Pump Inhibitor Lansoprazole Esomeprazole Pantoprazole 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This manuscript has been prepared with funding from unrestricted educational grant from ALTANA Pharma AG. The authors of this manuscript have no direct or indirect financial interest in ALTANA, nor have they received any direct honorarium or payment to undertake this work. As a clinical research organisation undertaking phase I clinical trials, SocraTec R&D has undertaken projects involving products of other pharmaceutical companies that also market proton pump inhibitors. Editorial support was provided by Rx Communications Ltd.


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Copyright information

© Adis Data Information BV 2006

Authors and Affiliations

  • Henning Blume
    • 1
    Email author
  • Frank Donath
    • 1
  • André Warnke
    • 1
  • Barbara S. Schug
    • 1
  1. 1.SocraTec R&D GmbHOberurselGermany

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