Effect of enzyme induction on the disposition of lorcainide in rats following intravenous and oral administration.

The pharmacokinetics of a single dose of lorcainide (4.5 mg/kg) was studied in rats pretreated with phenobarbital following intravenous and oral administration of lorcainide. In control rats, the total blood clearance of lorcainide was 30 ml/kg/min and the bioavailability was 14%. Pretreatment with phenobarbital increased the apparent oral clearance and reduced the bioavailability about 2fold. However, the pretreatment had a negligible effect on the systemic clearance following intravenous administration. Thus, enzyme induction increases the first-pass metabolism of lorcainide but does not alter the metabolism of drug which is in the systemic circulation.