Alterations of drug metabolism in rats exposed to cigarette smoke

In male rats exposed to cigarette smoke, antipyrine clearance was enhanced to the same extent as has been observed in human cigarette smokers. The activity of aryl hydrocarbon hydroxylase, a representative microsomal mixed function oxidase, was increased significantly in lung and kidney of smoke-exposed rats compared with controls. The activity of this enzyme in the liver, however, was not altered by cigarette smoke. Although aryl hydrocarbon hydroxylase activity in extrahepatic tissues was significantly enhanced after cigarette smoke exposures, the total drug metabolizing capacity of these tissues remained trivial compared with that of the liver. Hence, extrahepatic drug metabolism is unlikely to account for enhanced antipyrine elimination in cigarette smokers. The present study has established an animal model for studying the changes produced by cigarette smoke which result in enhanced drug metabolism in man.