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Editor,—I read with interest the recent article by Parkman et al(Gut1998;42:243–50) who reported on the effects of H2 receptor antagonists and omeprazole on interdigestive gastroduodenal motility and concluded that these drugs have a motor stimulant effect. This conclusion, however, could be invalidated by the unsatisfactory study design. The basal fasting period of 30 minutes prior to administration of the drug is very short when one considers that the mean duration of the cycle of the interdigestive migrating motor complex is at least three times as long1; the 30 minute observation period after drug administration is also quite short. Parkman and colleagues could have recorded the phase III that frequently occurs spontaneously when the stress caused by the insertion of the probe has lessened. In addition, omeprazole was given before the insertion of the manometric probe so that no control period was recorded in these subjects. These biases could raise some perplexing questions about the real effectiveness of these acid suppressants in stimulating interdigestive gastroduodenal motility. However, this is a real effect as has been previously and repeatedly demonstrated for ranitidine,2 famotidine,3nizatidine,4 and particularly for omeprazole.5 Unfortunately these studies were not cited by Parkman et al.
The hypothesis of cholinergic activity put forward to explain the strange motor effects of these acid suppressants could be valid for only a few H2 receptor antagonists. The most probable explanation is that acid suppression removes the inhibition exerted by acid on the initiation of phase III by motilin, as can be inferred from the close relation between the interdigestive motor and secretory activities of the stomach.6 However, as some authors have found an increase in plasma motilin after the administration of famotidine,3 I believe that a study on plasma motilin concentrations after the administration of these drugs, especially omeprazole, is desirable in an attempt to clarify the mechanism underlying this unexpected effect of these acid suppressants.
Editor,—We appreciate Professor Bortolotti’s comments by on our article. Our study showed that therapeutic doses of ranitidine, famotidine, and omeprazole, which suppress gastric acid secretion, affect both gastric motility and gastric emptying. Each agent delayed gastric emptying despite an increase in postprandial antral contractility as assessed using antral manometry, electrogastrography, and dynamic antral scintigraphy. Interestingly, these agents also stimulated antral phase III migrating motor complexes in the fasting state. In this letter, we address some of the comments raised by Professor Bortolotti.
The study was designed primarily to assess the affects of histamine type II receptor antagonists (H2RAs) on postprandial gastric emptying. We also simultaneously recorded electrogastrography, antroduodenal manometry, and dynamic antral scintigraphy to determine the mechanisms of altered gastric emptying. The study design included a 30 minute period to observe the effects of the gastric acid suppressants on fasting gastric motility to use as appropriate reference values for the postprandial effects. We agree that the 30 minute periods were relatively short to study the fasting period fully, with its 90 minute recurrent fasting migrating motor complexes. As our study was a four way cross over study, the effects of gastric acid suppression were compared, not only with the time periods before the administration of the study drug, but also with appropriate placebo controlled arms in the same subject. Omeprazole was given orally as there is not an intravenous form in the United States. The effects of omeprazole were compared only with the placebo arm. Professor Bortolotti notes that our findings have been confirmed by several other investigators.
Our study was designed to see whether the cholinergic properties of ranitidine seen in vitro1-1 could be seen in vivo. We compared the effects of ranitidine, an H2RA with cholinergic activity, with famotidine, an H2RA with little cholinergic activity, and with omeprazole, a proton pump inhibitor with no known cholinergic activity. We found that the effects of the gastric acid suppressants (ranitidine, famotidine, and omeprazole) were all similar, suggesting the effects seen were due to gastric acid suppression, rather than to selective properties of ranitidine. With the results of our studies, further investigation of the mechanism of gastric acid suppression on gastric motility can be undertaken. Professor Bortolotti suggests a study on plasma motilin concentrations after the administration of these drugs. We would also suggest measuring serum gastrin and somatostatin concentrations as these are also affected by gastric acid suppression and might mediate some of the gastric motor effects seen with gastric acid suppressants. Finally, one would want to monitor gastric pH during the study to help determine the degree of acid suppression with each of these agents. These points are addressed in the discussion section of our manuscript.
We thank Professor Bortolotti for his comments and the chance to address them. Professor Bortolotti has made many contributions to the relationship between gastric acid suppression and gastric motility, not only in normal subjects as our study, but also in gastric pathophysiology such as duodenal ulcer, gastric ulcer, and non-ulcer dyspepsia.
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