title: Multiple Dose Pharmacokinetics and Safety of Sulcardine Sulfate in Healthy Chinese Male Subjects: An Open-Label Phase I Clinical Study.
abstract: BACKGROUND
  Sulcardine sulfate is a novel antiarrhythmic agent with mechanism of action as a multi-ion channel blocker. Preclinical studies in animal models have demonstrated that sulcardine sulfate is efficacious in atrial and ventricular arrhythmias, and consequently, leads to the prevention of sudden cardiac death.
  
  
  OBJECTIVE
  This study was conducted in healthy Chinese male subjects to investigate the pharmacokinetic profile and safety of sulcardine sulfate after repeated oral dose administration at 200, 400, and 800 mg for 5 days.
  
  
  METHODS
  Thirty-three male subjects were enrolled in this study. In the multiple dose phase, sulcardine sulfate was administered orally twice at the interval of q12 h since day 3. Sulcardine sulfate plasma concentration was determined using a validated LC-MS/MS method. Safety was assessed using clinical evaluation and AE monitoring.
  
  
  RESULTS
  In this repeated dose study, pharmacokinetic parameters (Cmax, AUC(0-t),and Css_av)increased with the increase in dose (the dose ratio of the three cohorts was 1:2:4, while the ratio of Cmaxand AUC(0-t)at day 1 was around 1:4:9 and 1:4:6, respectively), but in a non-linear fashion. The accumulation ratio at steady state (AR) of 200, 400, and 800 mg dose level was 1.18, 1.69, and 2.13, respectively, indicating that sulcardine sulfate has a modest accumulation upon repeated dose administration. Monitoring of pre-dose plasma concentrations on days 6, 7, and 8 for each dose level indicated that steady state was achieved at day 6 after three-day repeated dosing.
  
  
  CONCLUSIONS
  Pharmacokinetic characteristics of sulcardine sulfate were shown to be non-linear, with the modest accumulation upon repeated dosing, and sulcardine sulfate was safe and well tolerated.
authors.affiliation: Emergency Ward, Shanghai Xuhui Central Hospital and Zhongshan-Xuhui Hospital, Fudan University and Shanghai Clinical Center, Chinese Academy of Science, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Central Laboratory, Shanghai Xuhui Central Hospital and Zhongshan-Xuhui Hospital, Fudan University and Shanghai Clinical Center, Chinese Academy of Science, Shanghai, China.
authors.forename: Hong-Jie
authors.initials: HJ
authors.lastname: Qian
authors.affiliation: Central Laboratory, Shanghai Xuhui Central Hospital and Zhongshan-Xuhui Hospital, Fudan University and Shanghai Clinical Center, Chinese Academy of Science, Shanghai, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Xin
authors.affiliation: Central Laboratory, Shanghai Xuhui Central Hospital and Zhongshan-Xuhui Hospital, Fudan University and Shanghai Clinical Center, Chinese Academy of Science, Shanghai, China.
authors.forename: Meng-Qi
authors.initials: MQ
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Dong-Ying
authors.initials: DY
authors.lastname: Lu
authors.affiliation: Central Laboratory, Shanghai Xuhui Central Hospital and Zhongshan-Xuhui Hospital, Fudan University and Shanghai Clinical Center, Chinese Academy of Science, Shanghai, China.
authors.forename: Jie-Mei
authors.initials: JM
authors.lastname: Jin
authors.affiliation: Central Laboratory, Shanghai Xuhui Central Hospital and Zhongshan-Xuhui Hospital, Fudan University and Shanghai Clinical Center, Chinese Academy of Science, Shanghai, China.
authors.forename: Gang-Yi
authors.initials: GY
authors.lastname: Liu
authors.affiliation: Central Laboratory, Shanghai Xuhui Central Hospital and Zhongshan-Xuhui Hospital, Fudan University and Shanghai Clinical Center, Chinese Academy of Science, Shanghai, China.
authors.forename: Jing-Ying
authors.initials: JY
authors.lastname: Jia
authors.affiliation: Department of Cardiology, Shanghai Xuhui Central Hospital and Zhongshan-Xuhui Hospital, Fudan University and Shanghai Clinical Center, Chinese Academy of Science, Shanghai, China.
authors.forename: Hong-Chao
authors.initials: HC
authors.lastname: Zheng
authors.affiliation: Central Laboratory, Shanghai Xuhui Central Hospital and Zhongshan-Xuhui Hospital, Fudan University and Shanghai Clinical Center, Chinese Academy of Science, Shanghai, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Shanghai Xuhui Central Hospital and Zhongshan-Xuhui Hospital, Fudan University and Shanghai Clinical Center, Chinese Academy of Science, Shanghai, China. zhufu@xh.sh.cn.
authors.forename: Fu
authors.initials: F
authors.lastname: Zhu
authors.affiliation: Central Laboratory, Shanghai Xuhui Central Hospital and Zhongshan-Xuhui Hospital, Fudan University and Shanghai Clinical Center, Chinese Academy of Science, Shanghai, China. yliu@shxh-centerlab.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood*; D019540:Area Under Curve; D002681:China; D004305:Dose-Response Relationship, Drug; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D013463:Sulfuric Acid Esters / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood*; D055815:Young Adult
chemical_list: D000889:Anti-Arrhythmia Agents; D013463:Sulfuric Acid Esters; C558473:sulcardine sulfate