Alteration of in vivo zoxazolamine metabolism by carbon monoxide in normal and polycyclic hydrocarbon-treated immature male rats.

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.