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Eur J Drug Metab Pharmacokinet. 2017 Jun;42(3):453-459. doi: 10.1007/s13318-016-0360-3.

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

Author information

1
Central Laboratory, Shanghai Xuhui Central Hospital / Zhongshan - Xuhui Hospital, Fudan University / Shanghai Clinical Center, Chinese Academy of Sciences, Shanghai, 200031, China.
2
Department of Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai, 201203, China.
3
Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, 430071, China.
4
Department of Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai, 201203, China. ypwang@mail.shcnc.ac.cn.

Abstract

BACKGROUND AND OBJECTIVES:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

PMID:
27402487
DOI:
10.1007/s13318-016-0360-3
[Indexed for MEDLINE]

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