Comparison of acid inhibition by either oral high‐dose ranitidine or omeprazole

Abstract

SUMMARY 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.

A Glass of Water Immediately Increases Gastric pH in Healthy Subjects

“…Although PPIs are the antisecretory drugs of choice for GERD, they are not considered good candidates for treatment of very short episodes because of the rather long lag time needed to increase intragastric pH [4 [13]. Indeed, our study showed that PPIs required longer time to increase gastric pH above 4 compared to ranitidine, and this finding is compatible with results reported by others [9][10][11][12][14][15][16]. However, our results are in contrast to studies showing that gastric pH failed to rise above 4 in the majority of subjects after PPI treatment during a 6-h period [9,13].…”

“…Many agents are currently available for the treatment of heartburn, including antacids, H 2 -receptor antagonists (H 2 RAs), and proton pump inhibitors (PPIs) [7]. PPIs have been established to be potent inhibitors during chronic administration [8]; however, H 2 RAs are reported to have a faster onset of antisecretory activity than that of PPIs [9][10][11].…”

Early effects of lafutidine or rabeprazole on intragastric acidity: which drug is more suitable for on-demand use?

“…During this early period, lafutidine had a faster onset of action and more strongly inhibited intragastric acid secretion than did rabeprazole, in both the fasting and postprandial subjects. These results support the findings of previous studies by Khoury et al, 10 Arnestad et al, 11 Hedenstrom et al, 12 Hurlimann et al, 13 Chassany et al, 14 and Abe et al, 15 showing that H 2 Fig. 2.…”

Does long-term medication with a proton pump inhibitor induce a tolerance to H2 receptor antagonist?

“…3 Several clinical studies have suggested that the inhibitory effects of proton pump inhibitors (PPIs) on gastric acid secretion may be similar or more potent, when compared with H 2 receptor antagonists, without the development of tolerance. 4,5 Therefore, we recently examined the effi cacy of preanesthetic PPI in patients receiving H 2 receptor antagonist medication for more than 4 weeks and found that PPIs were effective in reducing gastric acidity and volume whereas H 2 receptor antagonists were not. 6 As proton pump inhibitors inhibit H + /K + -adenosine triphosphatase, the fi nal step in gastric acid secretion from the parietal cell, 7 tolerance to these agents may not be induced with chronic treatment.…”