Stimulatory effects of chlordiazepoxide, diazepam and oxazepam on the drug-metabolizing enzymes in microsomes.

5 days' exposure of rats to daily doses of 400 mg/kg body wt. of chlordiazepoxide, diazepam and oxazepam stimulated the microsomal metabolism in the liver, as evidenced by acceleration of both p-hydroxylation of aniline and hydroxylation of benzene. The effect was accompanied by an increased concentration of liver microsomal protein and by the development of tolerance to the drugs. Similar effects were found after exposure of rats to lower doses of the drugs. The metabolism of aniline in vivo in rats treated with chlordiazepoxide was accelerated; this was correlated with development of tolerance to these drugs. It is suggested that both the stimulation of microsomal metabolism and the development of tolerance are associated with the induction of microsomal drug-metabolizing enzymes.