Lutz R J, Dedrick R L, Tuey D, Sipes I G, Anderson M W, Matthews H B
Drug Metab Dispos. 1984 Sep-Oct;12(5):527-35.
Physiologic pharmacokinetic analysis of 4,4'-dichlorobiphenyl, 2,2',3,3',6,6'-hexachlorobiphenyl, and 2,2',4,4',5,5'-hexachlorobiphenyl is presented for the dog and monkey, and the results are compared with previous similar analyses for the rat and mouse. The normalized clearances (ml/min/kg body weight) vary considerably between the dog and the monkey; the rat and the mouse show less species variation. The equilibrium tissue-to-blood distribution ratios for parent and metabolite are generally similar for all four species. The fat compartment has the highest parent distribution ratio for all four species, and the metabolite distribution ratios are much smaller than the parent distribution ratios. Metabolism appears to be a prerequisite to urinary and biliary excretion for all three compounds in each species. Elimination from the body occurs predominantly by the fecal route. The 2,2',4,4',5,5'-hexachlorobiphenyl is more slowly metabolized than the 2,2',3,3',6,6'-isomer in all species, which supports the contention that two adjacent, unsubstituted carbon atoms on the biphenyl ring promote more rapid metabolism.
本文介绍了4,4'-二氯联苯、2,2',3,3',6,6'-六氯联苯和2,2',4,4',5,5'-六氯联苯在犬和猴体内的生理药代动力学分析，并将结果与之前对大鼠和小鼠的类似分析进行了比较。犬和猴之间的归一化清除率（毫升/分钟/千克体重）差异很大；大鼠和小鼠的种间差异较小。所有四种物种中母体和代谢物的平衡组织与血液分布比通常相似。脂肪隔室在所有四种物种中母体分布比最高，代谢物分布比远小于母体分布比。在每个物种中，代谢似乎是所有三种化合物经尿液和胆汁排泄的前提条件。从体内消除主要通过粪便途径进行。在所有物种中，2,2',4,4',5,5'-六氯联苯的代谢速度比2,2',3,3',6,6'-异构体慢，这支持了联苯环上两个相邻的未取代碳原子促进更快代谢的观点。
