SUMMARYThe 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 node 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 node 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 < 0.005). After 15 days, the acid suppression afforded by sufotidine 600 mg b.d. was significantly attenuated (P < 0.0005); this was associated with a rise in 24‐h plasma gastrin (P < 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.

中文翻译：

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安慰剂、舒福替丁 600 mg nocte 或 sufotidine 600 mg 每天两次给药 15 天对 24 小时胃内酸度和 24 小时血浆胃泌素的影响


摘要在一项双盲、随机、三向交叉研究中，在 12 名健康男性中研究了舒福替定的酸抑制作用，舒福替丁 600 毫克节点和舒福替丁 600 毫克 b.d. 在 15 天内给药。在每种方案给药的第 1 天和第 15 天，通过放射遥测测量每个受试者的 24 小时动态胃内酸度，并从每小时静脉血样中获得 24 小时血浆胃泌素概况。酸抑制计算为氢离子活性与时间曲线下面积相对于安慰剂观察到的减少，24 小时血浆胃泌素计算为血浆胃泌素浓度与时间曲线下的面积。在服用苏福替丁 600 mg 节点和苏福替丁 600 mg b.d. 给药的第 15 天期间，24 小时胃内酸度没有显着差异，但在给药的第 1 天和第 15 天，苏福替丁 600 mg nocte 比苏福替丁 600 mg b.d. 降低夜间酸度的程度更大（P < 0.005）。15 天后，舒福替丁 600 mg b.d. 提供的酸抑制显着减弱 （P < 0.0005）;这与 24 h 血浆胃泌素升高有关 （P < 0.001）。因此，对 H2 受体拮抗剂的酸抑制作用存在耐受性，并且起效迅速。我们认为耐受性是由 24 小时血浆胃泌素的时间相关升高介导的，但我们不能排除其他机制（例如 H2 受体的上调）也起作用的可能性。