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  • Title: The effects of 15 days of dosing with placebo, sufotidine 600 mg nocte or sufotidine 600 mg twice daily upon 24-hour intragastric acidity and 24-hour plasma gastrin.
    Author: Rogers MJ, Holmfield JH, Primrose JN, Johnston D.
    Journal: Aliment Pharmacol Ther; 1990; 4 Suppl 1():65-74. PubMed ID: 1983347.
    Abstract:
    The acid inhibitory effect of sufotidine, a potent, long-lasting, competitive H2-receptor antagonist, was studied in 12 healthy males in a double-blind, randomized, three-way cross-over study of the effect of placebo, sufotidine 600 mg nocte and sufotidine 600 mg b.d. given over 15 days. On day 1 and 15 of dosing with each regimen, each subject's 24-h ambulatory intragastric acidity was measured by radiotelemetry and 24-h plasma gastrin profiles were derived from hourly venous blood samples. Acid suppression was calculated as the decrease in the area under the curve of hydrogen ion activity vs time from that observed on placebo, and 24-h plasma gastrin calculated as the area under the curve of plasma gastrin concentration vs time. Twenty-four hour intragastric acidity during the fifteenth day of dosing with sufotidine 600 mg nocte and sufotidine 600 mg b.d. did not differ significantly, but on the first and fifteenth day of dosing nocturnal acidity was decreased to a greater extent by sufotidine 600 mg nocte than sufotidine 600 mg b.d. (P less than 0.005). After 15 days, the acid suppression afforded by sufotidine 600 mg b.d. was significantly attenuated (P less than 0.0005); this was associated with a rise in 24-h plasma gastrin (P less than 0.001). Thus, tolerance to the acid inhibitory effect of H2-receptor antagonists exists and is of rapid onset. We suggest that tolerance is mediated by the temporally associated rise in 24-h plasma gastrin, but we cannot exclude the possibility that other mechanisms, such as up-regulation of H2-receptors, also play a part.
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