Krevsky B, Hitchcock M
Drug Metab Dispos. 1977 Sep-Oct;5(5):451-3.
The effect of carbon monoxide exposure on the in vivo metabolism of zoxazolamine in normal (corn oil-treated) and 3,4-benzpyrene- and 3-methylcholanthrene-treated, immature, male rats was examined. Pre-exposure of the animals for 90 min followed by determination of the duration of drug action while the animals were maintained in the experimental atmosphere resulted in a qualitative difference in response between normal and polycyclic hydrocarbon-treated animals over the concentration range of 150-450 ppm CO. Corn oil-treated animals demonstrated a decreased duration of drug action when exposed to CO, indicating an increase in the bioavailability of drug for metabolism which may be a result of an increase in liver perfusion rates. In contrast, polycyclic hydrocarbon-treated animals demonstrated an increased duration of drug action on exposure to CO. The qualitative difference in response to CO exposure in the two groups of animals may be due to differences in the sensitivity of cytochrome P-450 and cytochrome P-448 with respect to complexing with CO or to lowered intracellular PO2; or to differences in the dependency on blood flow of the rate of in vivo metabolism of zoxazolamine.
研究了一氧化碳暴露对正常（玉米油处理）以及经3,4-苯并芘和3-甲基胆蒽处理的未成熟雄性大鼠体内唑沙仑代谢的影响。在将动物置于实验环境中之前，先让其暴露90分钟，然后测定药物作用持续时间。结果显示，在150 - 450 ppm一氧化碳浓度范围内，正常动物和多环烃处理动物的反应存在质的差异。玉米油处理的动物在暴露于一氧化碳时，药物作用持续时间缩短，这表明药物代谢的生物利用度增加，这可能是肝脏灌注率增加的结果。相反，多环烃处理的动物在暴露于一氧化碳时，药物作用持续时间延长。两组动物对一氧化碳暴露反应的质的差异可能是由于细胞色素P - 450和细胞色素P - 448与一氧化碳结合的敏感性不同，或者是细胞内氧分压降低；也可能是唑沙仑体内代谢速率对血流的依赖性不同所致。
