Maiorino R M, Sipes I G, Gandolfi A J, Brown B R, Lind R C
Anesthesiology. 1981 May;54(5):383-9. doi: 10.1097/00000542-198105000-00007.
Since CF3CH2Cl and CF2CHCl are probably the products of reactive intermediates formed during the reductive metabolism of halothane (CF3CHClBr), factors affecting their in vitro and in vivo formation were investigated. In vitro studies with rat hepatic microsomes showed that CF3CH2Cl and CF2CHCl are produced by cytochrome P-450 mediated reductive pathways which were inhibited by the presence of CO. Under conditions of exposure known to promote halothane hepatotoxicity in phenobarbital treated rats (1 per cent halothane, 14 per cent oxygen), the hepatic and blood concentrations of the volatile metabolites were enhanced. Central venous levels of the volatile metabolites were much higher than he concentration in peripheral vessels. The CF3CH2Cl/CF2CHCl ratio in blood was approximately three, whereas the ratio in vitro was almost unity. Liver levels of the two volatile metabolites greatly exceeded the blood levels, but interestingly they were present in equivalent concentrations. The differences in the ratio of CF3CH2Cl to CF2CHCl may be explained by the fact that CF2CHCl is further degraded under oxidative conditions, whereas CF3CH2Cl appears relatively stable. Measurement of these metabolic products in patients undergoing halothane anesthesia may permit rapid detection of an unusually high level of halothane biotransformation along its hepatotoxic pathway.
由于CF3CH2Cl和CF2CHCl可能是氟烷（CF3CHClBr）还原代谢过程中形成的反应性中间体的产物，因此对影响它们在体外和体内形成的因素进行了研究。用大鼠肝微粒体进行的体外研究表明，CF3CH2Cl和CF2CHCl是由细胞色素P - 450介导的还原途径产生的，CO的存在会抑制该途径。在已知能促进苯巴比妥处理的大鼠发生氟烷肝毒性的暴露条件下（1%氟烷，14%氧气），挥发性代谢产物的肝脏和血液浓度会升高。挥发性代谢产物的中心静脉水平远高于外周血管中的浓度。血液中CF3CH2Cl/CF2CHCl的比值约为3，而体外比值几乎为1。两种挥发性代谢产物的肝脏水平大大超过血液水平，但有趣的是它们的浓度相当。CF3CH2Cl与CF2CHCl比值的差异可能是由于CF2CHCl在氧化条件下会进一步降解，而CF3CH2Cl似乎相对稳定。对接受氟烷麻醉的患者进行这些代谢产物的测量，可能有助于快速检测出沿其肝毒性途径的氟烷生物转化异常高水平。
