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Reversal of the tolerance phenomenon by the intermittent administration of a histamine H2‐receptor antagonist
Author(s) -
Takahashi Morio,
Katayama Yasumi
Publication year - 2010
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2010.06308.x
Subject(s) - medicine , helicobacter pylori , antagonist , oral administration , crossover study , histamine , anesthesia , gastroenterology , ambulatory , receptor , pathology , alternative medicine , placebo
Background and Aim: The attenuated antisecretory activity of H2‐receptor antagonists (H2RA) during continuous administration is referred to as the tolerance phenomenon. A previous study indicated that Helicobacter pylori ( H. pylori ) infection prevents the occurrence of tolerance to H2RA. In the present study, we investigated whether intermittent (every other day) administration prevents the tolerance phenomenon in H. pylori ‐negative patients. Methods: Ten H. pylori ‐negative, healthy volunteers were included in the study. All of the patients underwent two courses of H2RA (lafutidine) administration: 21‐day continuous administration (every day), followed by 21‐day intermittent administration (every other day), with at least a 21‐day lafutidine‐free period between the first and second courses. All of the patients were examined by ambulatory intragastric pH monitoring five times: before medication, and on days 1 and 21 of the first (continuous) and second (intermittent) courses of lafutidine (10 mg b.d.) in a crossover fashion. Results: The continuous administration of lafutidine had a significantly attenuated, acid‐suppressing effect in H. pylori ‐negative patients, and showed evidence of the tolerance phenomenon. However, the tolerance phenomenon was not observed through intermittent administration. Conclusions: These results demonstrated that in H. pylori ‐negative patients, tolerance to H2RA, induced by continuous lafutidine administration, was reversed by subsequent intermittent administration.