Ikeda G J, Sapienza P P
Pharmacokinetics and Metabolism Branch, Center for Food Safety and Applied Nutrition, Food and Drug Administration, Laurel, MD 20708, USA.
Food Chem Toxicol. 1995 May;33(5):409-21. doi: 10.1016/0278-6915(95)00001-i.
Tissue distribution, excretion and metabolism studies of pentachloroanisole (PCA), an environmental metabolite of pentachlorophenol (PCP), were conducted in the beagle dog and miniature pig following single oral doses (25 mg/kg) of radiolabelled PCA. PCA was readily demethylated by both species, with a half-life of 5-8 min. The resultant PCP was the major metabolite in dogs and pigs. In the dog, an average of 21.9% of the administered radiolabel was excreted in the urine and 62.3% in the faeces during a 7-day period. Of the tissues analysed, an average of 3.2% of the radiolabel remained in the liver, and blood and muscle accounted for averages of 3.0 and 2.3%, respectively, of the dose. Free and conjugated PCP were found in the urine of dogs; no PCA or tetrachlorohydroquinone (TCH) were found. In dog faeces, PCP and a trace of polar material were observed; no PCA was excreted in dog faeces. In the miniature pig, an average of 25.8% of the administered radiolabel was excreted in the urine and 32.0% in the faeces during a 2-wk period. An average of 4.4% of the radiolabel was found in the liver, 8.8% in the blood, 7.1% in the muscle and 6.4% in the fat. In pig urine, PCP and conjugated PCP were the only metabolites observed; no PCA or TCH was found. Pig faeces contained a trace of unchanged PCA; PCP and polar metabolites were also found. Since pig tissues retained a sizeable residue 2 wk after a single dose of PCA, various agents were used in an attempt to decrease the tissue level of radiolabel in pigs; anion exchange resin was found to be the most effective.
在比格犬和小型猪单次口服放射性标记的五氯茴香醚（PCA）（25毫克/千克）后，开展了五氯苯酚（PCP）的环境代谢物五氯茴香醚的组织分布、排泄和代谢研究。两种动物体内的PCA均易于脱甲基，半衰期为5 - 8分钟。生成的PCP是犬和猪体内的主要代谢物。在犬中，在7天的时间里，平均21.9%的给药放射性标记经尿液排泄，62.3%经粪便排泄。在所分析的组织中，平均3.2%的放射性标记留存于肝脏，血液和肌肉中的放射性标记分别平均占给药剂量的3.0%和2.3%。在犬的尿液中发现了游离和结合态的PCP；未发现PCA或四氯对苯二酚（TCH）。在犬的粪便中，观察到了PCP和微量极性物质；犬粪便中未排泄出PCA。在小型猪中，在2周的时间里，平均25.8%的给药放射性标记经尿液排泄，32.0%经粪便排泄。在肝脏中发现平均4.4%的放射性标记，血液中为8.8%，肌肉中为7.1%，脂肪中为6.4%。在猪的尿液中，观察到的唯一代谢物是PCP和结合态PCP；未发现PCA或TCH。猪的粪便中含有微量未变化的PCA；也发现了PCP和极性代谢物。由于单次给予PCA后2周猪的组织中仍残留相当数量的放射性标记，因此使用了各种药剂试图降低猪体内放射性标记的组织水平；发现阴离子交换树脂最为有效。
