Digestive Diseases and Sciences

, Volume 35, Issue 8, pp 976–983 | Cite as

Tolerance to oral H2-receptor antagonists

  • C. H. Wilder-Smith
  • T. Ernst
  • M. Gennoni
  • B. Zeyen
  • F. Halter
  • H. S. Merki
Original Articles


The acid-inhibitory action of H2-receptor antagonists was shown to decrease after one to two weeks of dosing in healthy volunteers. This tolerance was evaluated in three randomized, placebo-controlled trials with the H2-receptor antagonists famotidine, 40 mg given after the evening meal for 28 days; ranitidine, 300 mg four times a day for seven days followed by 300 mg at night until day 28; and ranitidine, 300 mg three times a day vs 300 mg at night for 14 days. Continuous 24-hr pH monitoring with glass electrodes was performed under fed conditions. The median 24-hr pH decreased from 3.2 on day 1 with famotidine 40 mg to 1.9 on day 28 (P<0.0012). After seven days of dosing with ranitidine 300 mg four times a day the median 24-hr pH dropped from 5.0 on day 1 to 3.0 on day 7 (P<0.001) and then to 2.2 with ranitidine 300 mg at night on day 28. With ranitidine 300 mg three times a day the median 24-hr pH fell from 4.3 on day 1 to 2.4 on day 14 (P< 0.0005). With ranitidine 300 mg at night the respective pH values were 2.5 and 1.8 (P< 0.003). Tolerance to H2-receptor antagonists given in a single evening dose was only evident during the night, whereas tolerance occurred throughout the day and night with the three- and four-times-a-day regimens. A large increase in the interindividual variability of pH response was seen during the nighttime.

Key words

24-hour pH-metry tolerance ranitidine famotidine acid inhibition pharmacodynamics H2-receptor antagonists 


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Copyright information

© Plenum Publishing Corporation 1990

Authors and Affiliations

  • C. H. Wilder-Smith
    • 1
  • T. Ernst
    • 1
  • M. Gennoni
    • 1
  • B. Zeyen
    • 1
  • F. Halter
    • 1
  • H. S. Merki
    • 1
  1. 1.Gastrointestinal Unit, Department of MedicineUniversity of Berne, InselspitalBerneSwitzerland

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