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Omeprazole induces gastric permeability to digoxin
M Gabello1, M C Valenzano, M Barr
1Lankenau Institute for Medical Research, 100 Lancaster Avenue, Wynnewood, PA 19096, USA.
Digestive Diseases and Sciences
|June 11, 2009
Summary
Omeprazole causes a gastric leak, allowing larger drugs like digoxin to enter the bloodstream faster. This drug interaction may increase blood levels, posing a clinical risk.
Area of Science:
- Pharmacology
- Gastroenterology
- Drug Metabolism
Background:
- Omeprazole is known to induce gastric leaks.
- The clinical implications of this leak, especially for drugs with narrow therapeutic windows, require further investigation.
Purpose of the Study:
- To investigate the effect of omeprazole on gastric permeability to drugs with narrow therapeutic windows.
- To assess the specificity of the omeprazole-induced gastric leak.
Main Methods:
- Ussing chamber experiments were performed using rat gastric corpus.
- The permeability of the gastric mucosa to digoxin and phenytoin in the presence of omeprazole was measured.
Main Results:
- Omeprazole significantly increased the gastric mucosal permeability to digoxin (780 MW).
- Omeprazole did not affect the permeability to phenytoin (252 MW), indicating specificity of the leak.
- The observed leak could lead to elevated blood digoxin levels.
Conclusions:
- Omeprazole induces a specific, tight-junctional gastric leak that affects larger molecules.
- This omeprazole-induced leak, combined with its inhibition of cytochrome P450 enzymes, may increase the risk of drug toxicity.
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