SUMMARYTwenty‐four‐hour intragastric acidity and 24‐h plasma gastrin concentration were measured on four occasions in six groups of eight healthy male subjects. Each group was studied before dosing, and on days 1, 15 and 29 of dosing with a standard regimen of an H2‐receptor antagonist (cimetidine 800 mg node, nizatidine 300 mg node, famotidine 40 mg node, ranitidine 150 mg node, ranitidine 150 mg b.d., or ranitidine 300 mg node). On the first day of dosing, each regimen using an H2‐antagonist caused a significant decrease of intragastric acidity and a significant rise of plasma gastrin concentration. Continued dosing with each Hi‐antagonist resulted in a significant attenuation of the effect on intragastric acidity, which was most noticeable overnight, but no significant change of plasma gastrin concentration. When grouped together, median integrated nocturnal acidity for the 48 subjects was 485, 35, 67 and 117 mmol. h/L for days 0, 1, 15 and 29, respectively, associated with a median nocturnal integrated plasma gastrin concentration of 46, 72, 79 and 73 pmol. h/L.The study demonstrates that a degree of tolerance develops during continued dosing with all available H2‐receptor antagonists, and that this phenomenon occurs during sustained elevation of plasma gastrin concentration.

中文翻译：

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西咪替丁、尼扎替丁、法莫替丁或雷尼替丁常规给药 29 天内的耐受性


摘要在 6 组 8 名健康男性受试者中，测量了 4 次 24 小时胃内酸度和 24 小时血浆胃泌素浓度。每组在给药前以及给药的第 1 天、第 15 天和第 29 天使用 H2 受体拮抗剂的标准方案（西咪替丁 800 mg 淋巴结、尼扎替定 300 mg 淋巴结、法莫替丁 40 mg 淋巴结、雷尼替丁 150 mg 淋巴结、雷尼替丁 150 mg b.d. 或雷尼替丁 300 mg 淋巴结）。在给药的第一天，使用 H 2 拮抗剂的每种方案都导致胃内酸度显着降低和血浆胃泌素浓度显着升高。继续服用每种 Hi 拮抗剂导致对胃内酸度的影响显着减弱，这在一夜之间最为明显，但血浆胃泌素浓度没有显着变化。当归为一组时，48 名受试者的中位综合夜间酸度为 485 、 35 、 67 和 117 mmol。第 0 天、第 1 天、第 15 天和第 29 天的 h/L 与中位夜间综合血浆胃泌素浓度为 46、72、79 和 73 pmol 相关。研究表明，在持续服用所有可用的 H2 受体拮抗剂期间会产生一定程度的耐受性，并且这种现象发生在血浆胃泌素浓度持续升高期间。