Effect of amiodarone and desethylamiodarone on the pharmacokinetics of antipyrine in the rat.

The effect of amiodarone on hepatic drug metabolism in vivo was examined in the rat using antipyrine as a model substrate. Pretreatment with oral amiodarone hydrochloride, 100 mg/kg/day, for 5 days resulted in a 19% reduction in antipyrine clearance and a 22% increase in half-life. The administration of single oral doses of amiodarone hydrochloride, 100 mg/kg, 1 or 5 hr prior to antipyrine administration had no significant effect on antipyrine pharmacokinetics. The administration of a single intravenous dose of amiodarone hydrochloride, 50 mg/kg, reduced antipyrine clearance by 32% and increased the half-life by 46%. The desethyl metabolite of amiodarone was also found to reduce antipyrine clearance (21%) after a single oral dose of 100 mg/kg.