The novel proton pump inhibitor pantoprazole elevates intragastric pH for a prolonged period when administered under conditions of stimulated gastric acid secretion in the gastric fistula dog

Abstract

The duration of intragastric pH-elevation upon administration of the novel H+K(+)-ATPase inhibitor pantoprazole and its pharmacodynamic interaction with H2 receptor blockade was assessed in the gastric fistula dog using the intragastric 24 hour pH-metry. Gastric acid secretion was stimulated by s.c. pentagastrin infusion. Group A received i.v. saline (controls), group B once an i.v. bolus of pantoprazole and group C twice the H2-receptor antagonist famotidine. Group D received the doses of famotidine and pantoprazole used in groups B and C. The intragastric pH-elevating effect of pantoprazole was not prolonged but, in fact, significantly shortened by the pretreatment with famotidine. Moreover, this effect depended on the pretreatment-dose of famotidine. The results underline that substituted benzimidazoles like pantoprazole need to be chemically activated in the acidic compartment of the parietal cell to produce a sustained intragastric pH-elevation. With regard to the potential therapeutic implication of these observations it is speculated that pantoprazole may be most effective in patients with high gastric acid secretion but may display reduced duration of intragastric pH-elevation under conditions of low acid secretion when acid blockade is not required.