title: Oral Bioavailability and Mass Balance Studies of a Novel Anti-arrhythmic Agent Sulcardine Sulfate in Sprague-Dawley Rats and Beagle Dogs.
abstract: OBJECTIVE
  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.
authors.affiliation: Central Laboratory, Shanghai Xuhui Central Hospital / Zhongshan - Xuhui Hospital, Fudan University / Shanghai Clinical Center, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: You-Li
authors.initials: YL
authors.lastname: Lu
authors.affiliation: Central Laboratory, Shanghai Xuhui Central Hospital / Zhongshan - Xuhui Hospital, Fudan University / Shanghai Clinical Center, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Shui-Jun
authors.initials: SJ
authors.lastname: Li
authors.affiliation: Central Laboratory, Shanghai Xuhui Central Hospital / Zhongshan - Xuhui Hospital, Fudan University / Shanghai Clinical Center, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Gang-Yi
authors.initials: GY
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Xiao-Chuan
authors.initials: XC
authors.lastname: Li
authors.affiliation: Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, 430071, China.
authors.forename: Ding
authors.initials: D
authors.lastname: Yang
authors.affiliation: Central Laboratory, Shanghai Xuhui Central Hospital / Zhongshan - Xuhui Hospital, Fudan University / Shanghai Clinical Center, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Jing-Ying
authors.initials: JY
authors.lastname: Jia
authors.affiliation: Central Laboratory, Shanghai Xuhui Central Hospital / Zhongshan - Xuhui Hospital, Fudan University / Shanghai Clinical Center, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Meng-Qi
authors.initials: MQ
authors.lastname: Zhang
authors.affiliation: Central Laboratory, Shanghai Xuhui Central Hospital / Zhongshan - Xuhui Hospital, Fudan University / Shanghai Clinical Center, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Hong-Chao
authors.initials: HC
authors.lastname: Zheng
authors.affiliation: Central Laboratory, Shanghai Xuhui Central Hospital / Zhongshan - Xuhui Hospital, Fudan University / Shanghai Clinical Center, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yu
authors.affiliation: Central Laboratory, Shanghai Xuhui Central Hospital / Zhongshan - Xuhui Hospital, Fudan University / Shanghai Clinical Center, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Fu
authors.initials: F
authors.lastname: Zhu
authors.affiliation: 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.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Wang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000493:pharmacokinetics*; D001646:Bile / Q000737:chemistry; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004285:Dogs; D005243:Feces / Q000737:chemistry; D005260:Female; D051381:Rats; D017207:Rats, Sprague-Dawley; D013463:Sulfuric Acid Esters / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry / Q000379:methods; D014556:Urine / Q000737:chemistry
chemical_list: D000889:Anti-Arrhythmia Agents; D013463:Sulfuric Acid Esters; C558473:sulcardine sulfate