Twenty-four-hour intragastric pH: tolerance within 5 days of continuous ranitidine administration

To investigate further the phenomenon of pharmacological tolerance to H2-receptor antagonists, we undertook a study of the antisecretory effect of ranitidine with continuous daily administration.

A total of 28 healthy male volunteers were given ranitidine 150 mg q.i.d. for 5 days. Twenty-four-hour intragastric pH monitoring was performed predosing and on days 1 and 5 of ranitidine administration. Serial blood samples were collected on days 1 and 5 of ranitidine administration for pharmacokinetics.

Mean 24-h intragastric pH was 2.62 predosing, 4.22 on day 1 of ranitidine administration and 3.28 on day 5 (p = 0.001, ranitidine day 1 vs. day 5). Intragastric pH was >3, 4, and 5 for 69.9%, 54.3%, and 35.9%, respectively, on day 1 of ranitidine administration and was 45.8%, 30.1%, and 20.8% on day 5 (p<0.005 for each comparison). Subjects' Helicobacter pylori status did not affect the antisecretory effect of ranitidine. There was no alteration in ranitidine pharmacokinetics to account for its reduced antisecretory effect.

This study has demonstrated a statistically significant reduction in the antisecretory effect of ranitidine within 5 days of continuous administration which is not explained by altered ranitidine pharmacokinetics. This is further evidence for the development of a form of pharmacological tolerance to an H2-receptor antagonist within a few days of continuous daily dosing.