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.