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

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 40 mg/kg. Beagle dogs were also orally and intravenously dosed at 10 mg/kg. Both [3H]-labeled sulcardine and unlabeled sulcardine were given to rats. Feces, urine and bile were collected at 0–72 h 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 absorbed in both rats and dogs after oral administration. The mass balance data indicated that sulcardine was widely metabolized in rats after oral administration.