LOSS OF ACID SUPPRESSION DURING DOSING WITH H2-RECEPTOR ANTAGONISTS

  • 1 January 1990
    • journal article
    • research article
    • Vol. 4, 15-27
Abstract
The suppression of intragastric acidity with H2-receptor antagonists may diminish with repeated administration. To assess the degree and dose-dependence of this tolerance after short-term dosing, two doses of the H2-receptor antagonists, ranitidine (300 mg nocte or q.d.s.) and sufotidine (300 mg or 600 mg b.d.), were given to healthy volunteers for 1 and 2 weeks, respectively. After 1 and 7 days of dosing with ranitidine 300 mg q.d.s. the median 24-h and night-time pH, measured by continuous 24-h pH-metry, dropped from 3.7 to 2.2 and 5.8 to 3.2, respectively (P < 0.0001 for both). The decline in median pH with ranitidine 300 mg nocte was only significant during the night (from 4.1 to 2.9) (P < 0.04). There was little change in plasma gastrin concentrations between days 1 and 7 with either dosage. With sufotidine 300 mg b.d. and 600 mg b.d. for 1 and 14 days, the median 24-h pH fell from 3.7 to 2.1 and from 4.6 to 2.6, respectively (P < 0.0001). The equivalent medians for the night decreased from 6.3 to 2.3 and from 6.6 to 3.1 (P < 0.0001). Gastrin concentrations did not change after 14 days of dosing with sufotidine 300 mg b.d., but increased significantly during dosing with sufotidine 600 mg b.d. (P < 0.001). Significant tolerance developed in 7-14 days and it seemed to show some dose relationship. The mechanisms behind tolerance and the role of gastrin are discussed, but remain unclear.

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