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Omeprazole Induces Gastric Permeability to Digoxin

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Abstract

Previous animal and patient-based studies have shown that omeprazole induces a transepithelial paracellular gastric leak. This study reports on the potential for an omeprazole-induced leak of drugs with narrow therapeutic windows. Ussing chamber experiments investigated the effects of omeprazole on rat gastric corpus permeability to the drugs, digoxin and phenytoin. Digoxin (780 MW) permeated the gastric mucosa at an accelerated rate in the presence of omeprazole. This leak could contribute to dangerous elevations of blood digoxin levels in certain situations. Omeprazole was found to have no effect on the flux rate of phenytoin (252 MW). The tight-junctional leak generated by omeprazole thus exhibits specificity to the types of molecules it allows to permeate through the gastric mucosa. This leak may pose a clinical danger by increasing drug uptake into the bloodstream, a phenomenon which would act synergistically with the effect of omeprazole on inhibiting liver cytochrome P450s that remove drugs from the bloodstream, thereby elevating drug blood levels.

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Abbreviations

PPI:

Proton pump inhibitor

TLC:

Thin-layer chromatography

LSC:

Liquid scintillation counting

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Acknowledgments

We would like to thank the GI fellows, Keith R. Kearney, D.O. and Kevin R. Wolov, D.O., for their helpful input and for sharing their medical expertise. This work was supported by the Sharpe/Strumia Foundation.

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Authors and Affiliations

  1. Lankenau Institute for Medical Research, 100 Lancaster Avenue, Wynnewood, PA, 19096, USA

    M. Gabello, M. C. Valenzano & J. M. Mullin

  2. Department of Biology, Saint Joseph’s University, Philadelphia, PA, USA

    M. Gabello

  3. Department of Medicine, Lankenau Hospital, Wynnewood, PA, USA

    M. Barr

  4. Department of Chemistry, Saint Joseph’s University, Philadelphia, PA, USA

    P. Zurbach

  5. Division of Gastroenterology, Lankenau Hospital, Wynnewood, PA, USA

    J. M. Mullin

Authors
  1. M. Gabello
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  2. M. C. Valenzano
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  3. M. Barr
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  4. P. Zurbach
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  5. J. M. Mullin
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Correspondence to J. M. Mullin.

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Gabello, M., Valenzano, M.C., Barr, M. et al. Omeprazole Induces Gastric Permeability to Digoxin. Dig Dis Sci 55, 1255–1263 (2010). https://doi.org/10.1007/s10620-009-0851-z

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  • DOI: https://doi.org/10.1007/s10620-009-0851-z

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