Loss of acid suppression during dosing with H2-receptor antagonists.
Loss of acid suppression during dosing with H2-receptor antagonists.
复制标题
使用 H2 受体拮抗剂给药期间酸抑制作用丧失。
DOI：
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发表时间：
1990
影响因子：
7.6
通讯作者：
Merki Hs
中科院分区：
文献类型：
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作者：
Clive H. Wilder;Fred Halter;T. Ernst;M. Gennoni;B. Zeyen;L. Varga;Roehmel Jj;Merki Hs
H2受体拮抗剂对胃内酸度的抑制作用可能随着重复给药而减弱。为了评估短期给药后这种耐受性的程度和剂量依赖性，两个剂量的H2受体拮抗剂雷尼替丁（300 mg单次或q.d.s.）和舒福替丁（300 mg或600 mg b.d.），分别给予健康志愿者1周和2周。雷尼替丁300 mg q.d.s.给药1天和7天后，通过连续24小时pH测定法测量的24小时和夜间pH值中位数分别从3.7降至2.2和5.8降至3.2（两者P均小于0.0001）。雷尼替丁300 mg/kg组的中位pH值仅在夜间显著下降（从4.1降至2.9）（P <0.04）。有血浆胃泌素浓度变化不大，第1和第7天之间的任何剂量。舒福替丁300 mg b.d.和600 mg b.d.第1天和第14天，24小时pH中位数分别从3.7降至2.1和从4.6降至2.6（P <0.0001）。夜间等效中位数从6.3降至2.3，从6.6降至3.1（P <0.0001）。舒福替丁300 mg b.d.给药14天后胃泌素浓度没有变化，但在舒福替丁600 mg b.d.给药期间显著增加。（P <0.001）。在7-14天内产生了显著的耐受性，似乎显示出一定的剂量关系。耐受性背后的机制和胃泌素的作用进行了讨论，但仍不清楚。
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 less than 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 less than 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 less than 0.0001). The equivalent medians for the night decreased from 6.3 to 2.3 and from 6.6 to 3.1 (P less than 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 less than 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.