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  • Title: Tolerance during 8 days of high-dose H2-blockade: placebo-controlled studies of 24-hour acidity and gastrin.
    Author: Smith JT, Gavey C, Nwokolo CU, Pounder RE.
    Journal: Aliment Pharmacol Ther; 1990; 4 Suppl 1():47-63. PubMed ID: 1983346.
    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.
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