Rennick B, Ziemniak J, Smith I, Taylor M, Acara M
J Pharmacol Exp Ther. 1984 Feb;228(2):387-92.
Renal tubular transport and renal metabolism of [14C]cimetidine (CIM) were investigated by unilateral infusion into the renal portal circulation in chickens (Sperber technique). [14C]CIM was actively transported at a rate 88% that of simultaneously infused p-aminohippuric acid, and its transport was saturable. The following organic cations competitively inhibited the tubular transport of [14C]CIM with decreasing potency: CIM, ranitidine, thiamine, procainamide, guanidine and choline. CIM inhibited the transport of [14C]thiamine, [14C]amiloride and [14C]tetraethylammonium. During CIM infusion, two renal metabolites, CIM sulfoxide and hydroxymethylcimetidine, were found in urine. When CIM sulfoxide was infused, its transport efficiency was 32% and not saturable. CIM sulfoxide did ot inhibit the simultaneous renal tubular transport of p-aminohippuric acid or tetraethylammonium. CIM is transported by the organic cation transport system and the kidney metabolizes CIM. Transport of CIM and other cationic drugs could produce a drug interaction to alter drug excretion.
通过向鸡的肾门静脉循环进行单侧输注（斯珀伯技术），研究了[14C]西咪替丁（CIM）的肾小管转运和肾脏代谢。[14C]CIM的主动转运速率为同时输注的对氨基马尿酸的88%，且其转运是可饱和的。以下有机阳离子以递减的效力竞争性抑制[14C]CIM的肾小管转运：CIM、雷尼替丁、硫胺素、普鲁卡因胺、胍和胆碱。CIM抑制[14C]硫胺素、[14C]阿米洛利和[14C]四乙铵的转运。在输注CIM期间，尿液中发现了两种肾脏代谢物，CIM亚砜和羟甲基西咪替丁。当输注CIM亚砜时，其转运效率为32%，且不饱和。CIM亚砜不抑制对氨基马尿酸或四乙铵同时进行的肾小管转运。CIM通过有机阳离子转运系统进行转运，且肾脏会代谢CIM。CIM和其他阳离子药物的转运可能会产生药物相互作用，从而改变药物排泄。
