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

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.