Comparison of the effect of carbon monoxide and of hypoxic hypoxia. I. In vivo metabolism, distribution and action of hexobarbital

Abstract

Previous experiments had shown that carbon monoxide inhalation prolonged the in vivo response zoxazolamine. However, CO was clearly less potent than an equivalent level of hypoxia induced by inhalation of lowered O2 content (hypoxic hypoxia). The present study revealed that both CO and hypoxic hypoxia also prolonged the pharmacologic response to a drug of vastly different structure and site of action, i.e., hexobarbital. In this case, CO was approximately equipotent to hypoxic hypoxia in prolonging sleeping time. In spite of a number of significant effects of the two types of hypoxia on factors such as rate of peritoneal absorption, distribution into the brain and brain sensitivity to the drug, their relative potencies in prolonging sleeping time appeared to reflect adequately their relative effects on in vivo rate of metabolism. This conclusion was based on their equipotencies in decreasing the rate of disappearance of hexobarbital from the blood. The observation that hypoxia induced by CO had no greater effect on hexobarbital metabolism than hypoxia induced by oxygen deprivation suggests that the binding of CO to cytochrome P-450 is not important in drug metabolism in vivo. CO would appear to act solely by inducing tissue hypoxia.