Rao G S, Grumley J O
Pharmacol Ther Dent. 1978;3(2-4):101-9.
Single anesthetic (11.5 mmole/kg) and nonanesthetic (4.6 mmole/kg) doses of 1-14C-halothane were administered separately to control and phenobarbital-pretreated rats by the intraperitoneal route. Tissue distribution and covalent binding of the anesthetic agent in the liver, lung, and kidney were determined at 4 and 24 hours after administration. Histopathological examination of the tissues revealed that halothane produced necrosis only in the livers of phenobarbital-pretreated rats and only after a period of 24 hours following the anesthetic dose. The lung and kidney appeared normal in all test animals. The liver was the major organ for the uptake, metabolism, and covalent binding of halothane metabolites to tissue proteins. Although similar metabolic activity was observed in the kidney and lung, toxic levels of the halothane metabolites were apparently not attained in these extrahepatic tissues in either control or phenobarbital-pretreated rats.
通过腹腔注射途径，分别向对照大鼠和经苯巴比妥预处理的大鼠给予单剂量麻醉剂（11.5毫摩尔/千克）和非麻醉剂量（4.6毫摩尔/千克）的1-¹⁴C-氟烷。给药后4小时和24小时测定麻醉剂在肝脏、肺和肾脏中的组织分布及共价结合情况。组织的组织病理学检查显示，氟烷仅在经苯巴比妥预处理的大鼠肝脏中产生坏死，且仅在给予麻醉剂量24小时后出现。所有试验动物的肺和肾脏均表现正常。肝脏是氟烷代谢产物摄取、代谢及与组织蛋白共价结合的主要器官。尽管在肾脏和肺中观察到了类似的代谢活性，但在对照大鼠或经苯巴比妥预处理的大鼠的这些肝外组织中，显然未达到氟烷代谢产物的毒性水平。
