title: Omeprazole induces gastric permeability to digoxin.
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.
authors.affiliation: Lankenau Institute for Medical Research, 100 Lancaster Avenue, Wynnewood, PA 19096, USA.
authors.forename: M
authors.initials: M
authors.lastname: Gabello
authors.forename: M C
authors.initials: MC
authors.lastname: Valenzano
authors.forename: M
authors.initials: M
authors.lastname: Barr
authors.forename: P
authors.initials: P
authors.lastname: Zurbach
authors.forename: J M
authors.initials: JM
authors.lastname: Mullin
mesh_terms: D000818:Animals; D002855:Chromatography, Thin Layer; D004077:Digoxin / Q000494:pharmacology*; D004594:Electrophysiology; D005753:Gastric Mucosa / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D009853:Omeprazole / Q000494:pharmacology*; D010539:Permeability; D010672:Phenytoin / Q000494:pharmacology; D054328:Proton Pump Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019108:Tight Junctions / Q000187:drug effects*
chemical_list: D054328:Proton Pump Inhibitors; D010672:Phenytoin; D004077:Digoxin; D009853:Omeprazole