Cacini W, Keller M B, Grund V R
J Pharmacol Exp Ther. 1982 May;221(2):342-6.
The mechanisms involved in the excretion of the histamine H2-receptor antagonist cimetidine are as yet incompletely understood. The purpose of this study was to examine the interaction of cimetidine with incubated slices of dog kidney cortex. The results of time and concentration-dependent experiments by using 3H-labeled cimetidine demonstrated that the drug was accumulated without metabolism against a concentration gradient by a saturable process. Inhibition of uptake by cyanide and by incubation under a nitrogen atmosphere indicated energy dependence. Uptake of cimetidine by active cationic transport was likely inasmuch as both cyanine 863 and quinine blocked accumulation. However, a probenecid-sensitive component, accounting for about 20% of steady-state accumulation, also was identified. The lack of inhibitory action of p-aminohippuric acid and the cationic nature of the cimetidine molecule suggest the probenecid-sensitivity was not related to the renal organic anion mechanism. Further, probenecid inhibition was not due to a generalized cellular toxicity because maximally inhibitory concentrations of probenecid did not interfere with uptake of the cation tetraethylammonium.
组胺H2受体拮抗剂西咪替丁的排泄机制目前尚未完全明确。本研究旨在检测西咪替丁与犬肾皮质孵育切片的相互作用。使用3H标记的西咪替丁进行的时间和浓度依赖性实验结果表明，该药物通过一个可饱和过程逆浓度梯度积累且无代谢发生。氰化物以及在氮气环境下孵育对摄取的抑制表明其对能量的依赖性。鉴于花青863和奎宁均能阻断积累，西咪替丁可能通过主动阳离子转运摄取。然而，还鉴定出一个对丙磺舒敏感的成分，约占稳态积累的20%。对氨基马尿酸缺乏抑制作用以及西咪替丁分子的阳离子性质表明，丙磺舒敏感性与肾脏有机阴离子机制无关。此外，丙磺舒抑制并非由于普遍的细胞毒性，因为丙磺舒的最大抑制浓度并不干扰阳离子四乙铵的摄取。
