ALTERATION OF DRUG METABOLISM IN RATS AND MICE BY AN ENVIRONMENT OF CEDARWOOD

Mice housed tin red cedarwood shavings, pine shavings, ground corncob Ireated with (a) an ether extract of cedarwood, (b) cedrol. (c) or cedrene, exhibited reduced hypnotic effects to hexobarbital. These effects were due to induction of microsomal enzymes responsible for hexobarbital degradation as shown by (a) increased in vitro hexobarbital metabolism, I hi increased liver weight, id increased microsomal protein content and id) inhibition of the enhanced hexobarbital metabolism by ethionine prelrealmenl to inhibit protein synthesis. The effects are not due to physiological antagonism such as central nervous system stimulation. The constituents of cedarwood oil are effective inducers of aniline hydro xylase, sulfanilamide acetylase, Neoprontosil azoreductase, heptachlor epoxidase and zoxazolamine hydroxylase activity as evidenced by enhanced in vitro metab olism. They also hasten the removal of bishydroxycoumarin from the blood ol rats in vivo. The effective Constituents cedrol and cedrene are volatile hydrocarbons thai are effective inducers of microsomal enzymes via Ihe inhalation route of administration. © 1968 S. Karger AG, Basel.