OMEPRAZOLE PROMOTES PROXIMAL DUODENAL MUCOSAL BICARBONATE SECRETION IN HUMANS

The proton pump inhibitor, omeprazole, surprisingly resulted in higher rates of proximal duodenal mucosal bicarbonate secretion than previou sly reported using an H-2 receptor antagonist for gastric acid inhibit ion. Gastroduodenal perfusions were performed in healthy volunteers to evaluate whether this incidental finding is explained by more potent gastric acid inhibition by omeprazole or might be caused by the differ ent mode of drug action. Basal and stimulated gastric and duodenal bic arbonate secretion rates were measured in the same subjects in control experiments (n=17) and after pretreatment with high dose omeprazole ( n=17) and ranitidine (n=9), respectively, by use of a technique permit ting simultaneous measurements. Concentrations of bicarbonate were mea sured in the respective effluents by the method of back titration. Bot h omeprazole and ranitidine completely inhibited gastric acid secretio n (pH 6.9 v 6.8; p>0.05). Omeprazole caused higher rates of basal (mea n (SEM)) (597 (48) v 351 (39) mu mol/h; p<0.02) and vagally stimulated (834 (72) v 474 (66) mu mol/h; p<0.02), but not acid stimulated (3351 (678) v 2550 (456) mu mol/h; p>0.05) duodenal bicarbonate secretion c ompared with control experiments. Also the combination of omeprazole a nd ranitidine increased (p=0.05) duodenal bicarbonate secretion, while ranitidine alone caused no change in either basal or stimulated secre tion. In the stomach basal as well as vagally stimulated bicarbonate s ecretion was independent of the means of acid inhibition. These result s show that the proton pump inhibitor, omeprazole, promotes proximal d uodenal mucosal bicarbonate secretion apparently independent of its ga stric acid inhibitory effect. The mechanism of action remains speculat ive.