Oral Bioavailability and Mass Balance Studies of a Novel Anti-arrhythmic Agent Sulcardine Sulfate in Sprague-Dawley Rats and Beagle Dogs.

Abstract

Sulcardine sulfate is a newly developed candidate drug used to control arrhythmias. The aim of this research was to investigate the pharmacokinetics, bioavailability and excretion characteristics of sulcardine in animals. Sprague-Dawley rats were orally and intravenously given sulcardine at 20 and 40mg/kg. Beagle dogs were also orally and intravenously dosed at 10mg/kg. Both [3H]-labeled sulcardine and unlabeled sulcardine were given to rats. Feces, urine and bile were collected at 0-72h for mass balance study. The contents of unlabeled sulcardine and radioactivity in samples were determined by a validated LC-MS/MS method and by liquid scintillation counting, separately. Sulcardine was rapidly eliminated in rats after dosing. The oral bioavailability was 34-35% in rats, while a higher exposure was observed in dogs (bioavailability=62.7%). More than 90% of dosed sulcardine was recovered, and approximately 20-40% of the dose excreted into urine as the original form, and the remaining was found in feces and bile, most of which (about 40%) was transformed into metabolites. No difference was observed between sexes. Metabolism may occur to a large extent after oral administration in rats but to a smaller extent in dogs. Sulcardine was extensively absorbedin both rats and dogs after oral administration. The mass balance data indicated that sulcardine was widely metabolized in rats after oral administration.