Induction of disopyramide N-dealkylation by phenobarbital and disopyramide in rat liver

An in vitro assay for the determination of the activity of disopyramide-N-dealkylation was developed. This reaction was concluded to be catalyzed by the liver microsomal, cytochrome P-450 centered monooxygenase system. Phenobarbital enhanced the N-dealkylation of disopyramide four fold, and disopyramide itself 1.6 fold, whereas methylcholanthrene was without effect. Disopyramide also increased ethoxycoumarin deethylation 1.6 fold, and had a slight increasing effect on the activity of epoxide hydratase, but did not affect the activities of glutathione S-transferase or UDPglucuronosyltransferase.