Omeprazole Induces Gastric Permeability to Digoxin

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...

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Bibliographic Details
Published in:Digestive diseases and sciences 2010-05, Vol.55 (5), p.1255-1263
Main Authors: Gabello, M, Valenzano, M. C, Barr, M, Zurbach, P, Mullin, J. M
Format: Article
Language:English
Subjects:
Animals
Biochemistry
Biological and medical sciences
Chromatography, Thin Layer
Clopidogrel
Digestive system
Digoxin
Digoxin - pharmacology
Electrophysiology
Feeding. Feeding behavior
Fundamental and applied biological sciences. Psychology
Gastric Mucosa - drug effects
Gastroenterology
Health aspects
Hepatology
Hydrogen-Ion Concentration
In Vitro Techniques
Male
Medical research
Medical sciences
Medicine
Medicine & Public Health
Medicine, Experimental
Omeprazole
Omeprazole - pharmacology
Oncology
Original Article
Permeability
Pharmacology. Drug treatments
Phenytoin
Phenytoin - pharmacology
Proton Pump Inhibitors - pharmacology
Rats
Rats, Sprague-Dawley
Tight Junctions - drug effects
Transplant Surgery
Vertebrates: anatomy and physiology, studies on body, several organs or systems
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Summary: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.
ISSN:0163-2116
1573-2568
DOI:10.1007/s10620-009-0851-z