Ghantous H N, Fernando J, Gandolfi A J, Brendel K
Department of Anesthesiology, University of Arizona, Tucson 85724.
Drug Metab Dispos. 1990 Jul-Aug;18(4):514-8.
The biotransformation of halothane was studied using liver slices. Precision-cut Hartley male guinea pig liver slices (1 cm diameter; 250-300 microns thick) were incubated in sealed roller vials containing supplemented Krebs-Henseleit buffer at 37 degrees C under different O2 tensions (2.5, 21, and 95%). After a 1-hr preincubation, halothane was vaporized in the vial producing a 1.9 mM medium concentration. Halothane metabolites (Br-, trifluoroacetic acid, F-) were measured at 2, 4, and 6 hr. Viability of the incubated slices was verified by determining intracellular K+ content and levels of cytochrome P-450, which were maintained under 95% O2 atmosphere but decreased with lower O2 tensions (2.5%). The highest fluoride production was 300 +/- 22 pmol/mg slice weight/6 hr at low O2 tension (2.5%). Defluorination decreased with increasing O2 tension to undetectable levels under 95% O2. Production of the oxidative metabolite, trifluoroacetic acid, was highest at 95% O2 (2.35 +/- 0.17 nmol/mg slice weight/6 hr). Trifluoroacetic acid production decreased with decreasing O2 tension. Br- production was the highest at 21% O2 (1.8 +/- 0.13 nmol/mg slice weight/6 hr). Production of Br- was not dependent on the O2 tension. The guinea pig slices are capable of biotransforming halothane (oxidative/reductive); therefore, this in vitro system appears suitable for studying the biotransformation of halothane.
使用肝切片研究了氟烷的生物转化。将精确切割的哈特利雄性豚鼠肝切片（直径1厘米；厚250 - 300微米）在密封的滚瓶中于37℃、不同氧气张力（2.5%、21%和95%）下，在含有补充了的克雷布斯 - 亨泽莱特缓冲液中孵育。预孵育1小时后，将氟烷在瓶中汽化，使培养基浓度达到1.9 mM。在2小时、4小时和6小时测量氟烷代谢物（Br -、三氟乙酸、F -）。通过测定细胞内K +含量和细胞色素P - 450水平来验证孵育切片的活力，细胞色素P - 450水平在95%氧气气氛下保持稳定，但在较低氧气张力（2.5%）下会降低。在低氧气张力（2.5%）下，最高氟化物生成量为300±22 pmol/毫克切片重量/6小时。脱氟作用随着氧气张力增加而降低，在95%氧气下降至不可检测水平。氧化代谢物三氟乙酸的生成在95%氧气下最高（2.35±0.17 nmol/毫克切片重量/6小时）。三氟乙酸生成量随着氧气张力降低而减少。Br -生成在21%氧气下最高（1.8±0.13 nmol/毫克切片重量/6小时）。Br -的生成不依赖于氧气张力。豚鼠切片能够对氟烷进行生物转化（氧化/还原）；因此，这个体外系统似乎适合用于研究氟烷的生物转化。
