Intravenous and oral lorcainide: assessment of central nervous system toxicity and antiarrhythmic efficacy.
Twenty-eight subjects underwent evaluation of drug toxicity and antiarrhythmic efficacy with oral and intravenous lorcainide. Lorcainide, a new type 1C antiarrhythmic drug, has an active metabolite, norlorcainide, which accumulates after oral but not significantly after intravenous administration. Group 1 consisted of 14 subjects who received intravenous lorcainide with an initial bolus of 2 mg/kg at a rate of 2 mg/min followed by 0.14 mg/min or 200 mg/24 hours. The lorcainide level after bolus was 0.432 micrograms/ml and fell to 0.178 micrograms/ml at 4 to 6 hours despite constant drug infusion. Prior work has demonstrated no detectable norlorcainide levels after intravenous infusion. Group II consisted of 14 subjects who received oral lorcainide, 100 mg orally every 8 hours. Mean lorcainide levels were 0.287 micrograms/ml and mean norlorcainide levels were 0.377 micrograms/ml. Only 2 of 12 subjects in group I experienced headache, dizziness, or sleep disturbance, compared to 12 of 14 subjects in group II (p less than 0.01). Intravenous lorcainide has a lower incidence of central nervous system side effects than oral lorcainide. These effects may be attributable to the accumulation of the norlorcainide metabolite with oral therapy.
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000503:physiopathology; D044482:Benzeneacetamides; D002490:Central Nervous System / Q000187:drug effects*; D005260:Female; D006352:Heart Ventricles / Q000503:physiopathology; D006801:Humans; D007263:Infusions, Parenteral; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D010880:Piperidines / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*
D044482:Benzeneacetamides; D010880:Piperidines; C031145:norlorcainide; C015970:lorcainide