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Relative potency of proton-pump inhibitors—comparison of effects on intragastric pH

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European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Aim

Comparative potency of proton-pump inhibitors (PPIs) is an important clinical issue. Most available trials have compared the different PPIs at one or a few selected specific dosages, making it difficult to derive quantitative equivalence dosages. Here we derived PPI dose equivalents based on a comprehensive assessment of dose-dependent effects on intragastric pH.

Methods

All available clinical studies reporting the effects of PPIs on mean 24-h intragastric pH were sought from electronic databases including Medline. Studies included were restricted to those targeting the Caucasian population, and healthy volunteers or gastroesophageal reflux disease (GERD) patients. The dose-effect relationships for mean 24-h intragastric pH and for percentage of time with pH > 4 in 24 h were analyzed for each PPI using pharmacodynamic modeling with NONMEM and a model integrating all available data.

Results

Fifty-seven studies fulfilled the inclusion criteria. Based on the mean 24-h gastric pH, the relative potencies of the five PPIs compared to omeprazole were 0.23, 0.90, 1.00, 1.60, and 1.82 for pantoprazole, lansoprazole, omeprazole, esomeprazole, and rabeprazole, respectively. Compared with healthy volunteers, patients with GERD needed a 1.9-fold higher dose and Helicobacter pylori-positive individuals needed only about 20% of the dose to achieve a given increase in mean 24-h intragastric pH.

Conclusion

The present meta-analysis provides quantitative estimates on clinical potency of individual PPIs that may be helpful when switching between PPIs and for assessing the cost-effectiveness of specific PPIs. However, our estimates must be viewed with caution because only a limited dose range has been tested and not exactly the same study conditions were applied for the different substances.

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Acknowledgements

Part of the cost for compilation of this analysis was provided by an educational grant from Eisai-Deutschland GmbH.

Conflict of interest

None of the authors has any conflict of interest that might potentially bias this work.

Author information

Authors and Affiliations

  1. Institute of Pharmacology of Natural Products and Clinical Pharmacology, University of Ulm, Helmholtzstr. 20, 89081, Ulm, Germany

    Julia Kirchheiner & Silke Glatt

  2. Department of Pharmacology, Clinical Pharmacology, University of Cologne, Cologne, Germany

    Uwe Fuhr

  3. Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany

    Ulrich Klotz

  4. Department of Internal Medicine I, University of Halle, Halle, Germany

    Thomas Seufferlein

  5. Department of Clinical Pharmacology, Georg August University Göttingen, Göttingen, Germany

    Ingolf Meineke & Jürgen Brockmöller

Authors
  1. Julia Kirchheiner
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  2. Silke Glatt
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  3. Uwe Fuhr
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  4. Ulrich Klotz
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  5. Ingolf Meineke
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  6. Thomas Seufferlein
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  7. Jürgen Brockmöller
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Corresponding author

Correspondence to Julia Kirchheiner.

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Kirchheiner, J., Glatt, S., Fuhr, U. et al. Relative potency of proton-pump inhibitors—comparison of effects on intragastric pH. Eur J Clin Pharmacol 65, 19–31 (2009). https://doi.org/10.1007/s00228-008-0576-5

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  • DOI: https://doi.org/10.1007/s00228-008-0576-5

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