Abstract

Pretreatment of rats with phenobarbital, barbital, aminopyrine, phenylbutazone, orphenadrine and 3,4-benzpyrene causes a marked increase in the activity of various drug-metabolizing enzymes in the liver microsomes. Evidence is presented that phenobarbital induces the synthesis of these enzymes and stimulates liver protein synthesis. Administration of certain drugs enhances the ability of liver microsomes to metabolize the same or a closely related cornpound. Thus the administration of phenylbutazone, aminopyrine, 3,4-benzpyrene or phenobarbital will respectively increase the ability of rat liver microsomes to metabolize phenylbutazone, aminopyrine, 3,4-benzpyrene or hexobarbital. The ability of drugs to stimulate drugmetabolizing enzymes is paralleled in vivo by an accelerated rate of drug metabolism and by a shortened duration of drug action. Pretreatment of rats with several drugs shortened considerably the duration of zoxazolamine paralysis and hexobarbital hypnosis.