放射性标记五氯苯甲醚在大鼠和兔子体内的处置与代谢

Disposition and metabolism of radiolabelled pentachloroanisole in rats and rabbits.

作者信息

Ikeda G J, Sapienza P P, Warr P I

机构信息

Pharmacokinetics and Metabolism Branch, Food and Drug Administration, Laurel, MD 20708.

出版信息

Food Chem Toxicol. 1994 Dec;32(12):1137-46. doi: 10.1016/0278-6915(94)90129-5.

DOI:10.1016/0278-6915(94)90129-5

PMID:7813985

Abstract

Male Sprague-Dawley rats and New Zealand White rabbits were administered 14C-labelled pentachloroanisole (PCA) in corn oil by gavage as single doses of 25 mg/kg and were then placed in individual metabolism cages for as long as 4 days. Peak blood level of radioactivity occurred 6 hr after administration of the dose to rats and between 3 and 4 hr in rabbits; the blood elimination half-life ranged from 8 to 15 hr in rats and averaged 6 hr in rabbits. Rats excreted an average of 54.2% of the administered radiolabel in the urine and 32.4% in the faeces during the 96 hr following the dose; rabbits excreted an average of 84.2 and 13.1% of the radiolabel in the urine and faeces, respectively, during this time. Examination of the metabolites in the rat showed that 60% of the urinary radioactivity was attributable to tetrachlorohydroquinone (TCH), 3% to free pentachlorophenol (PCP) and 29% to conjugated PCP; faecal metabolites were PCP (85.7%), TCH (4.3%) and polar metabolite(s) (10%). In the rabbit, 58% of the urinary radioactivity was attributable to TCH, 8% to free PCP and 34% to conjugated PCP. Faecal metabolites consisted of PCP and conjugated material.

摘要

将雄性斯普拉格 - 道利大鼠和新西兰白兔经口灌胃给予溶于玉米油的14C标记五氯茴香醚（PCA），单剂量为25mg/kg，然后将它们置于个体代谢笼中长达4天。给大鼠给药后6小时出现放射性血药浓度峰值，给兔子给药后3至4小时出现峰值；大鼠的血药消除半衰期为8至15小时，兔子平均为6小时。给药后96小时内，大鼠尿中平均排出给药放射性标记物的54.2%，粪便中排出32.4%；在此期间，兔子尿中平均排出放射性标记物的84.2%，粪便中排出13.1%。对大鼠体内代谢物的检测表明，尿中60%的放射性归因于四氯对苯二酚（TCH），3%归因于游离五氯苯酚（PCP），29%归因于结合型PCP；粪便代谢物为PCP（85.7%）、TCH（4.3%）和极性代谢物（10%）。在兔子中，尿中58%的放射性归因于TCH，8%归因于游离PCP，34%归因于结合型PCP。粪便代谢物由PCP和结合物组成。