title: Tolerance to H2 receptor antagonist correlates well with the decline in efficacy against gastroesophageal reflux in patients with gastroesophageal reflux disease.
abstract: OBJECTIVE
  The attenuated antisecretory activity of H2 receptor antagonists (H2RA) during continuous administration is known as the tolerance phenomenon. The authors recently clarified that presence or absence of Helicobacter pylori infection influences the occurrence of the tolerance phenomenon. The aim of this study was to clarify whether tolerance to H2RA is correlated with attenuation of the inhibitory effect against gastroesophageal acid reflux in patients with gastroesophageal reflux disease (GERD).
  
  
  METHODS
  Ten male patients with GERD symptoms and abnormal gastroesophageal reflux were investigated by pH monitoring on days 1 and 15 of continuous oral famotidine administration at 20 mg twice daily, and H. pylori infection was examined using the urea breath test.
  
  
  RESULTS
  Intragastric and intraesophageal acidity were significantly decreased on the first day of famotidine administration, but then increased during the 15-day administration period in seven patients who were negative for H. pylori. In contrast, the efficacy of famotidine against gastric acid secretion and gastroesophageal acid reflux was not attenuated in three H. pylori-positive patients. The changes in GERD symptoms were correlated with the change in the degree of gastroesophageal reflux.
  
  
  CONCLUSIONS
  The presence or absence of tolerance to H2RA during 15-day administration is correlated with the efficacy for inhibition of gastroesophageal acid reflux.
authors.affiliation: Department of Gastroenterology and Hepatology, Shimane University, School of Medicine, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Furuta
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Adachi
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Komazawa
authors.forename: Takafumi
authors.initials: T
authors.lastname: Mihara
authors.forename: Masaharu
authors.initials: M
authors.lastname: Miki
authors.forename: Takane
authors.initials: T
authors.lastname: Azumi
authors.forename: Tomoo
authors.initials: T
authors.lastname: Fujisawa
authors.forename: Tomoko
authors.initials: T
authors.lastname: Katsube
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kinoshita
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D015738:Famotidine / Q000008:administration & dosage / Q000627:therapeutic use*; D005744:Gastric Acid / Q000378:metabolism; D005745:Gastric Acidity Determination; D005764:Gastroesophageal Reflux / Q000188:drug therapy* / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D016896:Treatment Outcome
chemical_list: D006635:Histamine H2 Antagonists; D015738:Famotidine