Tolerance during 8 days of high‐dose H2‐blockade: placebo‐controlled studies of 24‐hour acidity and gastrin

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Abstract
SUMMARY: 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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