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.
D000284:Administration, Oral; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D044482:Benzeneacetamides; D001682:Biological Availability; D004790:Enzyme Induction / Q000187:drug effects; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D010880:Piperidines / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D000889:Anti-Arrhythmia Agents; D044482:Benzeneacetamides; D010880:Piperidines; C015970:lorcainide