Selectivity of the cimetidine-induced alterations in the renal handling of organic substrates in humans. Studies with anionic, cationic and zwitterionic drugs.
Selectivity of the cimetidine-induced alterations in the renal handling of organic substrates in humans. Studies with anionic, cationic and zwitterionic drugs.
复制标题
西咪替丁诱导的人体肾脏处理有机底物的选择性改变。
DOI：
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发表时间：
1986
影响因子：
3.5
通讯作者：
A. Somogyi
中科院分区：
文献类型：
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作者：
J. V. Van Crugten;F. Bochner;J. Keal;A. Somogyi
西咪替丁通过抑制肾阳离子近端小管分泌，降低人体和体外制剂中有机阳离子普鲁卡因胺和n-乙酰普鲁卡因胺的肾清除率。本研究的目的是在人体中研究西咪替丁在改变三种不同有机离子作为原料药的肾脏处理方面的选择性：阴离子（头孢噻吩）、阳离子（雷尼替丁）和两性离子（头孢氨苄）。该研究在6名健康受试者中进行，这些受试者接受上述药物单次给药，同时接受和不接受长期西咪替丁给药。西咪替丁对头孢噻吩处置（包括肾脏清除率）无统计学显著性（P> 0.05）影响，但在给药后4 - 12小时内，雷尼替丁的肾脏清除率显著降低40%以上，同时雷尼替丁血浆浓度增加，消除半衰期延长。此外，头孢氨苄的肾脏清除率在1 - 2小时内被西咪替丁降低了27%，但头孢氨苄的血浆浓度和消除半衰期没有变化。这些发现证实了以下假设：西咪替丁介导的人体肾脏药物清除抑制对肾脏近端小管中常见的阳离子分泌转运机制具有选择性，而不是对肾功能的非特异性作用。
Cimetidine reduces the renal clearances of the organic cations procainamide and n-acetylprocainamide in humans and in vitro preparations by inhibition of renal cationic proximal tubular secretion. The aim of this study was to investigate in humans the selectivity of cimetidine in altering the renal handling of three different organic ions as drug substances: anion (cephalothin), cation (ranitidine) and zwitterion (cephalexin). The study was conducted in six healthy subjects who received the above drugs as single doses with and without chronic cimetidine administration. Cimetidine had no statistically significant (P greater than .05) effect on cephalothin disposition including renal clearance, but significantly reduced the renal clearance of ranitidine by over 40% between 4 and 12 hr after administration, with a concomitant increase in ranitidine plasma concentrations and elimination half-life prolongation. In addition, the renal clearance of cephalexin was reduced by cimetidine by 27% between 1 and 2 hr, but there was no change in cephalexin plasma concentrations and elimination half-life. These findings confirmed the hypothesis that cimetidine-mediated inhibition of renal drug clearance in humans is selective for a common cationic secretory transport mechanism in the proximal tubule of the kidney, rather than a nonspecific action on renal function.