Anderson M W, Eling T E, Lutz R J, Dedrick R L, Matthews H B
Clin Pharmacol Ther. 1977 Nov;22(5 Pt 2):765-73. doi: 10.1002/cpt1977225part2765.
The construction of a preliminary pharmacokinetic model for the distribution, long-term storage sites, excretion, and metabolism of selected polychlorinated biphenyls (PCBs) in the rat is described. Following intravenous administration of radioactive PCBs, several metaboiltes of each PCB isomer were detected in urine or feces, excreted primarily as glucuronide conjugates. The relative and absolute amount of metabolites excreted depended upon the degree of chlorination and the position of the chlorine on the biphenyl molecule. Concerning long-term storage sties, an unanticipated finding was accumulation in skin, as revealed by the particularly long half-life of the 6-CB isomer in skin. A flow diagram of the model is presented, as are the differential equations, solved by computer for a given dose schedule, for the individual mass balances on parent and metabolite in each of the compartments that represent the organs or regions in which the concentration is assumed to be uniform. Low-level, long-term doses of PCBs produce a variety of toxicologic symptoms which appear only after long-time exposure. Such models should be useful in explaining and predicting the toxicities induced by exposure to PCBs and similar contaminants and the time required to reach a steady-state tissue concentration for given long-term doses.
本文描述了大鼠体内选定多氯联苯（PCBs）的分布、长期储存部位、排泄和代谢的初步药代动力学模型的构建。静脉注射放射性多氯联苯后，在尿液或粪便中检测到每种多氯联苯异构体的几种代谢物，主要以葡萄糖醛酸结合物的形式排泄。排泄的代谢物的相对和绝对量取决于氯化程度和氯在联苯分子上的位置。关于长期储存部位，一个意外发现是在皮肤中积累，这通过6-氯联苯异构体在皮肤中特别长的半衰期得以揭示。给出了该模型的流程图，以及微分方程，通过计算机针对给定的剂量方案求解，以计算代表器官或区域（假设其中浓度均匀）的每个隔室中母体和代谢物的个体质量平衡。低水平、长期剂量的多氯联苯会产生各种毒理学症状，这些症状仅在长时间接触后才会出现。此类模型应有助于解释和预测接触多氯联苯及类似污染物所引发的毒性，以及给定长期剂量达到稳态组织浓度所需的时间。
