Famotidine and Omeprazole Both Induce Gastric Transmucosal Leak

Abstract

Background: Our group has recently published that proton pump inhibitors (PPIs) induce transmucosal, paracellular, bidirectional leakage in the gastric corpus epithelium to a wide range of molecules. Aim: This study was undertaken to determine if H-2 blocker medications also induce such leakage, or whether it is a result of specific inhibition of H + ,K + -ATPase. Methods: At the beginning and end of a dosage regimen of omeprazole or famotidine, healthy volunteers with no history of gastrointestinal disease consumed a (probe) solution of 100 gms of sucrose in 200 cc of water. Subsequently an 8 hr urine specimen was collected. The sucrose concentration in the urine specimen (mg/ml) multiplied by the total urine vol- ume equaled the amount of sucrose (mg) which leaked from the gastric lumen into the bloodstream. Results: Like omeprazole, famotidine was also able to induce significant transmucosal leakage across the mucosal barrier of the upper gastrointestinal tract. Famotidine-induced leakage exhibited a narrower time course than was observed with omeprazole. Conclusions: The fact that both classes of acid suppressive medications induce leak implies that leak results not from di- rect inhibition of the H + ,K + -ATPase, or from a side effect of omeprazole-like molecules, but is more generally related to the overall inhibition of acid secretion. The medical significance of such gastric leak is discussed.