DIFFERENTIAL INFLUENCE OF PHYSIOLOGICAL, PHARMACOLOGICAL AND PATHOLOGICAL ALTERATIONS ON HEPATIC AND EXTRAHEPATIC DRUG METABOLISM

Abstract

Factors known to influence hepatic drug metabolism were evaluated for their influence on drug metabolism in extrahepatic organs. The well-documented sex-related differences in drug metabolism in rat liver were not seen in either lung or kidney. Treatment of rats with phenobarbital elicited the expected increases in mixed function oxidase (MFO) parameters in liver without concomitant changes in these activities in lung and with only scattered and less marked changes in kidney. UDP-Glucuronyltransferase activity was undetectable toward two substrates in rabbit lung microsomes. Several activators which stimulated hepatic UDP-glucuronyltranferase several fold had no effect on the pulmonary enzyme. Treatment of rats with CCl4 inhibited the hepatic and pulmonary MFO systems in a quantitatively and temporally similar manner but was without effect on the renal system. Increases in hepatic and renal but not pulmonary UDP-glucuronyltransferase were observed after CCl4. Scurvy impaired most MFO activities in liver microsomes but evoked no change or much smaller changes in extrahepatic organs. It is concluded that some factors that influence hepatic drug metabolism produce similar effects in lung and kidney while the effects of other factors are organ-specific.