title: pH-feedback controlled infusions of ranitidine are no more effective than fixed-dose infusions in reducing gastric acidity and variability in antisecretory responses.
abstract: 1. The antisecretory responses to pH-feedback controlled (maximum dose 800 mg 24 h-1) and fixed-dose (0.25 mg kg-1 h-1) continuous infusions of ranitidine were compared in a randomised, placebo-controlled, cross-over study in 10 healthy male volunteers. 2. To assess tolerance during repeated dosing with ranitidine, the same infusion regimens were given before and after 6 days oral dosing with ranitidine 300 mg four times daily. 3. With the pH-feedback controlled infusion of ranitidine the median % time (interquartile range) with pH greater than 4 in the 24 h period was 57% (45-76) before and 23% (17-34) after 6 days oral dosing (P less than 0.001). The respective values with fixed-dose infusion were 51% (38-63) and 26% (15-32) (P less than 0.002). 4. The median 24 h doses (interquartile range) of ranitidine given by feedback-controlled infusion before and after 6 days oral dosing were 675 mg (542-728) and 749 mg (709-760), respectively (P less than 0.01). The dose of ranitidine given by fixed-rate infusion was 423 mg (393-502) on both study days (P less than 0.001 vs feedback infusion). 5. Plasma gastrin concentrations remained slightly elevated after 6 days of oral ranitidine dosing, whereas pancreatic polypeptide plasma levels remained unchanged. 6. The antisecretory efficacy of infusions of ranitidine is significantly decreased by circadian stimuli and tolerance. Individually-adapted infusions of high doses of ranitidine were not superior to fixed-dose infusion of 0.25 mg kg-1 h-1 in overcoming this variability.
authors.affiliation: Department of Medicine, University of Berne, Switzerland.
authors.forename: C H
authors.initials: CH
authors.lastname: Wilder-Smith
authors.forename: F
authors.initials: F
authors.lastname: Halter
authors.forename: W
authors.initials: W
authors.lastname: Häcki
authors.forename: H S
authors.initials: HS
authors.lastname: Merki
mesh_terms: D000328:Adult; D002940:Circadian Rhythm; D004064:Digestive System / Q000378:metabolism*; D005755:Gastrins / Q000097:blood*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007260:Infusion Pumps; D008297:Male; D010191:Pancreatic Polypeptide / Q000097:blood*; D011897:Random Allocation; D011899:Ranitidine / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D005755:Gastrins; D010191:Pancreatic Polypeptide; D011899:Ranitidine