title: Tolerance during 8 days of high-dose H2-blockade: placebo-controlled studies of 24-hour acidity and gastrin.
abstract: Simultaneous 24-h intragastric and plasma gastrin concentrations were measured in 36 healthy subjects, when receiving placebo (day 0) and on days 1 and 8 of dosing with either placebo (n = 8), or high-dose H2-blockade with either ranitidine 300 mg q.d.s. (n = 8), ranitidine 1200 mg o.m. (n = 8), or sufotidine 600 mg b.d. (n = 12). Triplicate placebo studies demonstrated good reproducibility for this technique, with no significant differences of acidity or plasma gastrin concentration between the studies. There was a decrease in the anti-secretory activity of all three high-dose H2-antagonist regimens on day 8, when compared with that observed on day 1. This occurred in the presence of sustained or increasing hypergastrinaemia. It is concluded that a degree of tolerance develops during continued H2-blockade, and that this could be due to increasing gastrin drive to the parietal cells.
authors.affiliation: Academic Department of Medicine, Royal Free Hospital School of Medicine, London, UK.
authors.forename: J T
authors.initials: JT
authors.lastname: Smith
authors.forename: C
authors.initials: C
authors.lastname: Gavey
authors.forename: C U
authors.initials: CU
authors.lastname: Nwokolo
authors.forename: R E
authors.initials: RE
authors.lastname: Pounder
mesh_terms: D000328:Adult; D004361:Drug Tolerance; D005744:Gastric Acid / Q000378:metabolism*; D005755:Gastrins / Q000097:blood*; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D010919:Placebos; D011899:Ranitidine / Q000097:blood / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
chemical_list: D005755:Gastrins; D006635:Histamine H2 Antagonists; D010880:Piperidines; D010919:Placebos; D014230:Triazoles; C062101:sufotidine; D011899:Ranitidine