Yonemitsu K
Forensic Sci Int. 1986 Aug-Sep;32(1):33-42. doi: 10.1016/0379-0738(86)90156-8.
Pharmacokinetic studies of paraquat in rabbits were performed using [methyl-14C]-paraquat. Plasma concentration of paraquat following i.v. administration to the rabbit was fitted to a 3-exponential function of pharmacokinetic analysis. Distribution and elimination were discussed on the basis of the 3-compartment open model system, which has a central and two peripheral compartments. Computer simulations of paraquat levels in each compartment indicated that the slow-uptake peripheral compartment contained a greater amount of paraquat than the central or the fast-uptake peripheral compartment. On the basis of the present results of the computer simulations in company with tissue distributions of paraquat reported by the other investigators, it is likely that the slow-uptake peripheral compartment contains the lung. In cases of paraquat-induced renal failures, the paraquat levels of the slow-uptake peripheral compartment were remarkably higher than in cases of normal renal functions. Histology of the rabbit tissues 7 days after i.v. administration of paraquat revealed that marked changes were observed only in the kidney, suggesting some renal failures induced by paraquat. In spite of the high concentration of paraquat, which was presumed with the computer simulations in this study, the rabbit lung showed a remarkable resistance to paraquat toxicity. The histology studies suggested the complexities of paraquat toxicity to the rabbit. The lung toxicity in the rabbit would be caused by not only the paraquat concentration in the lung but also some biochemical parameters in the tissue related to the mechanisms of paraquat toxicity.
使用[甲基-14C]百草枯对家兔进行了百草枯的药代动力学研究。家兔静脉注射百草枯后的血浆浓度符合药代动力学分析的三指数函数。基于三室开放模型系统（有一个中央室和两个外周室）讨论了分布和消除情况。计算机模拟各室中的百草枯水平表明，摄取缓慢的外周室所含百草枯的量比中央室或摄取快速的外周室更多。根据目前计算机模拟结果以及其他研究者报道的百草枯组织分布情况，摄取缓慢的外周室很可能包含肺。在百草枯诱发肾衰竭的情况下，摄取缓慢的外周室中的百草枯水平显著高于肾功能正常的情况。家兔静脉注射百草枯7天后的组织学检查显示，仅在肾脏观察到明显变化，提示百草枯诱发了一些肾衰竭。尽管根据本研究中的计算机模拟推测百草枯浓度很高，但家兔肺对百草枯毒性表现出显著抗性。组织学研究提示了百草枯对家兔毒性的复杂性。家兔的肺毒性不仅由肺中的百草枯浓度引起，还可能与组织中一些与百草枯毒性机制相关的生化参数有关。
