title: Diurnal secretory patterns and tolerance during individually titrated infusions of ranitidine.
abstract: BACKGROUND
  Gastric acid secretion in humans shows chronobiological patterns that modify the efficacy of antisecretory agents. The ability of individually titrated ranitidine infusions to overcome circadian patterns of gastric acidity and tolerance during prolonged dosing was assessed.
  
  
  METHODS
  Eleven healthy subjects were randomized to receive ranitidine infusions of up to 600 mg/24 hours by a pH feedback-regulated pump before and after 9 days of oral dosing with ranitidine, 300 mg four times daily, beginning either in the evening or in the morning in a cross-over, third party-blinded and placebo-controlled study design.
  
  
  RESULTS
  Mean 24-hour intravenous ranitidine doses given to attain the target pH of 4 were greater after 9 days of treatment with oral ranitidine than before in the morning and evening studies (P < 0.01). The median 24-hour pH decreased from 5.1 before to 3.6 after oral dosing in the morning study (P < 0.001) and from 4.4 to 2.8 in the evening study (P < 0.001). Before oral dosing of ranitidine, the time of pH > 4 in the evening and morning fasting periods was 71% and 84%, respectively (P < 0.05). After 9 days oral ranitidine, the respective results were 20% and 53% (P < 0.05).
  
  
  CONCLUSIONS
  The reduced responsiveness to ranitidine in the evening and the tolerance to ranitidine with repeated dosing were not overcome by individually titrated, high intravenous doses of ranitidine.
authors.affiliation: Department of Medicine, Inselspital, University of Berne, Switzerland.
authors.forename: H S
authors.initials: HS
authors.lastname: Merki
authors.forename: F
authors.initials: F
authors.lastname: Halter
authors.forename: C H
authors.initials: CH
authors.lastname: Wilder-Smith
mesh_terms: D000284:Administration, Oral; D000328:Adult; D002940:Circadian Rhythm / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004361:Drug Tolerance; D004435:Eating; D005215:Fasting; D005260:Female; D005745:Gastric Acidity Determination; D005755:Gastrins / Q000097:blood; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007260:Infusion Pumps; D007262:Infusions, Intravenous; D008297:Male; D010191:Pancreatic Polypeptide / Q000097:blood; D011863:Radioimmunoassay; D011899:Ranitidine / Q000008:administration & dosage* / Q000494:pharmacology; D013997:Time Factors
chemical_list: D005755:Gastrins; D006635:Histamine H2 Antagonists; D010191:Pancreatic Polypeptide; D011899:Ranitidine