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Tolerance to oral H2-receptor antagonists
C H Wilder-Smith1, T Ernst, M Gennoni
1Department of Medicine, University of Berne, Inselspital, Switzerland.
Digestive Diseases and Sciences
|August 1, 1990
Summary
Tolerance to H2-receptor antagonists like famotidine and ranitidine develops within weeks, diminishing their acid-inhibitory effects. This tolerance varied based on dosing frequency, impacting nighttime acid control more significantly with less frequent regimens.
Area of Science:
- Pharmacology
- Gastroenterology
Background:
- H2-receptor antagonists are commonly used to reduce stomach acid.
- Tolerance to the acid-inhibitory effects of these drugs can develop over time.
- Understanding tolerance is crucial for optimizing acid suppression therapy.
Purpose of the Study:
- To evaluate the development of tolerance to H2-receptor antagonists.
- To compare tolerance across different dosing regimens of famotidine and ranitidine.
- To assess the impact of tolerance on 24-hour gastric pH control.
Main Methods:
- Three randomized, placebo-controlled trials were conducted.
- Participants received famotidine (40 mg once daily) or ranitidine (300 mg multiple times daily or at night).
- Continuous 24-hour gastric pH monitoring was performed under fed conditions.
Main Results:
- Tolerance, indicated by decreased acid inhibition, was observed within 1-2 weeks for all regimens.
- Famotidine 40 mg showed a significant decrease in 24-hour pH from day 1 to day 28.
- Ranitidine regimens also demonstrated tolerance, with greater impact on nighttime pH and increased variability.
- Tolerance occurred throughout the day and night with multiple daily doses, but primarily at night with single evening doses.
Conclusions:
- Tolerance to H2-receptor antagonists develops with continued dosing.
- Dosing frequency influences the pattern and extent of tolerance.
- Single evening doses showed tolerance mainly at night, while multiple daily doses led to tolerance throughout the day and night.