title: Tolerance to famotidine and ranitidine treatment after 14 days of administration in healthy subjects without Helicobacter pylori infection.
abstract: OBJECTIVE
  The attenuated antisecretory activity observed during continuous administration of ranitidine has been described as tolerance. However, it remains unclear whether a similar phenomenon occurs with other histamine H2 receptor antagonists (H2RA). We investigated whether tolerance to famotidine, a stronger H2RA than ranitidine, occurs during long-term administration.
  
  
  METHODS
  Seven healthy male Japanese subjects without Helicobacter pylori infection participated in a randomized cross-over study in which ranitidine and famotidine were administered for 14 days with a 4-week wash-out period. We performed 24-h intragastric pH monitoring on the first and 14th days of administration of each drug, and measured serum gastrin and plasma drug concentrations on the first, seventh and 14th days.
  
  
  RESULTS
  The acid-inhibiting activity of ranitidine and famotidine declined during continuous administration. In particular, the potent nocturnal pH-increasing effect of the H2RA, which was observed on day 1, declined on day 14. Serum gastrin concentrations on day 14 were significantly lower than those on day 7, although plasma drug concentrations remained unchanged.
  
  
  CONCLUSIONS
  Tolerance to famotidine occurs during continuous administration for 14 days, as previously shown in ranitidine studies.
authors.affiliation: Department of Internal Medicine II, Shimane Medical University, Izumo, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Komazawa
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Adachi
authors.forename: Takafumi
authors.initials: T
authors.lastname: Mihara
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ono
authors.forename: Akira
authors.initials: A
authors.lastname: Kawamura
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Fujishiro
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kinoshita
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D018592:Cross-Over Studies; D004361:Drug Tolerance / Q000502:physiology*; D015738:Famotidine / Q000008:administration & dosage*; D005745:Gastric Acidity Determination; D005755:Gastrins / Q000097:blood / Q000187:drug effects; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000382:microbiology*; D016480:Helicobacter pylori; D006635:Histamine H2 Antagonists / Q000008:administration & dosage*; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007564:Japan; D008297:Male; D008875:Middle Aged; D011899:Ranitidine / Q000008:administration & dosage*; D012016:Reference Values; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D005755:Gastrins; D006635:Histamine H2 Antagonists; D015738:Famotidine; D011899:Ranitidine