BACKGROUND: High-dose once daily oral omeprazole dosing can inhibit acid secretion almost completely but several days elapse before maximum efficacy is established. The acid inhibitory effect obtained with high doses of a histamine H2-receptor antagonist is built up rapidly but has the tendency to fade--the term 'tolerance' has been applied to characterize this phenomenon. METHODS: To obtain more information on the dynamics of acid inhibition during prolonged dosing, we compared the acid suppressory effects of oral high-dose omeprazole with high-dose ranitidine. Twenty-eight healthy volunteers were randomly assigned to a 2-week dosing with omeprazole or ranitidine in a double-blind, double-dummy, parallel-group study design. Omeprazole was given as 1 capsule of 40 mg mane and ranitidine as 2 tabs of 150 mg q.d.s. The median 24-h pH, daytime pH and night-time pH were measured by ambulatory continuous 24-h pH metry on days -8, -6, 1, 2, 7 and 14. RESULTS:High reproducibility was observed for the two baseline acidity measurements. Ranitidine exerted its peak acid suppressant effect on day 1 of dosing; the degree of acid inhibition faded from day 2 to 7, with no significant change thereafter. The decline in antisecretory activity was more pronounced during the day than the night. In contrast, acid inhibition by omeprazole increased throughout the first week, and antisecretory activity was stable thereafter. Despite the considerable differences in median intragastric pH values at the end of the 14-day study, plasma gastrin levels were elevated to a similar degree with both medications. CONCLUSIONS: This study confirms the 'tolerance' phenomenon previously observed with high-dose histamine H2-receptor antagonist dosing. The dynamics with which it occurs exclude a typical exaggerated first-dose response. Prolonged high-dose histamine H2-receptor dosing compromises the feedback mechanism regulating gastrin release, whilst this is maintained during dosing with omeprazole.
RCT Entities:
BACKGROUND: High-dose once daily oral omeprazole dosing can inhibit acid secretion almost completely but several days elapse before maximum efficacy is established. The acid inhibitory effect obtained with high doses of a histamine H2-receptor antagonist is built up rapidly but has the tendency to fade--the term 'tolerance' has been applied to characterize this phenomenon. METHODS: To obtain more information on the dynamics of acid inhibition during prolonged dosing, we compared the acid suppressory effects of oral high-dose omeprazole with high-dose ranitidine. Twenty-eight healthy volunteers were randomly assigned to a 2-week dosing with omeprazole or ranitidine in a double-blind, double-dummy, parallel-group study design. Omeprazole was given as 1 capsule of 40 mg mane and ranitidine as 2 tabs of 150 mg q.d.s. The median 24-h pH, daytime pH and night-time pH were measured by ambulatory continuous 24-h pH metry on days -8, -6, 1, 2, 7 and 14. RESULTS: High reproducibility was observed for the two baseline acidity measurements. Ranitidine exerted its peak acid suppressant effect on day 1 of dosing; the degree of acid inhibition faded from day 2 to 7, with no significant change thereafter. The decline in antisecretory activity was more pronounced during the day than the night. In contrast, acid inhibition by omeprazole increased throughout the first week, and antisecretory activity was stable thereafter. Despite the considerable differences in median intragastric pH values at the end of the 14-day study, plasma gastrin levels were elevated to a similar degree with both medications. CONCLUSIONS: This study confirms the 'tolerance' phenomenon previously observed with high-dose histamine H2-receptor antagonist dosing. The dynamics with which it occurs exclude a typical exaggerated first-dose response. Prolonged high-dose histamine H2-receptor dosing compromises the feedback mechanism regulating gastrin release, whilst this is maintained during dosing with omeprazole.
Authors: Karen E Hansen; Andrea N Jones; Mary J Lindstrom; Lisa A Davis; Toni E Ziegler; Kristina L Penniston; Amy L Alvig; Martin M Shafer Journal: J Bone Miner Res Date: 2010-06-24 Impact factor: 6.741