西咪替丁的人体胎盘转运
Human placental transport of cimetidine.
作者信息
Schenker S, Dicke J, Johnson R F, Mor L L, Henderson G I
机构信息
Department of Medicine, University of Texas, Health Science Center, San Antonio.
出版信息
J Clin Invest. 1987 Nov;80(5):1428-34. doi: 10.1172/JCI113222.
This study addresses the mechanism of transport of the H2-receptor antagonist, cimetidine, by the human placenta. A 4-h recycling perfusion of a single placental cotyledon of normal, term, human placenta was used. At a maternal concentration of 1 microgram/ml, cimetidine clearance from the maternal circulation was 0.58 +/- 0.16 ml/min per g placenta, a rate about one third that of antipyrine. There was no evidence of cimetidine metabolism by the placenta. Transfer of cimetidine from maternal to fetal compartments showed no saturation kinetics and was not inhibited by putative carrier competitors. Cimetidine did not accumulate against a drug concentration gradient. Fetal clearance of cimetidine was similar to maternal clearance. Studies with placental apical vesicles confirmed lack of saturability of cimetidine transport and of its concentration within vesicles. Thus, (a) cimetidine is transported across the human placenta bidirectionally at a rate about one third that of antipyrine, (b) the drug is not metabolized by the placenta, and (c) the transport is a passive one.
本研究探讨了人胎盘转运H2受体拮抗剂西咪替丁的机制。采用对正常足月人胎盘的单个胎盘小叶进行4小时循环灌注的方法。当母体浓度为1微克/毫升时，西咪替丁从母体循环中的清除率为每克胎盘0.58±0.16毫升/分钟，约为安替比林清除率的三分之一。没有证据表明胎盘对西咪替丁进行代谢。西咪替丁从母体向胎儿区室的转运未表现出饱和动力学，也不受假定的载体竞争剂的抑制。西咪替丁不会逆药物浓度梯度蓄积。胎儿对西咪替丁的清除率与母体清除率相似。对胎盘顶端小泡的研究证实了西咪替丁转运及其在小泡内浓度缺乏饱和性。因此，（a）西咪替丁以约为安替比林三分之一的速率双向转运穿过人胎盘，（b）该药物不会被胎盘代谢，且（c）转运是被动的。
Zotero 插件