Pharmacokinetics, safety, and tolerability of sulcardine sulfate: an open-label, single-dose, randomized study in healthy Chinese subjects.
Sulcardine sulfate (Sul) is a novel anti-arrhythmic agent as a potential treatment for atrial fibrillation and ventricular arrhythmias. This study was conducted to investigate the pharmacokinetic profile, safety, and tolerability of Sul in healthy Chinese subjects. In this open-label, single-dose, randomized study, 10 healthy subjects were assigned to receive Sul doses of 200, 400, and 800 mg under fasting conditions (Cohorts A, B, and C, respectively) or 400 mg under fed conditions (Cohort D). The study incorporated a crossover design, separated by a seven-day washout period. Blood samples were collected before treatment and at successive time intervals up to 48 h after treatment. Sul concentrations in plasma samples were determined using a validated LC-MS/MS method. Tolerability was determined by clinical evaluation and adverse event (AE) monitoring. Pharmacokinetic results demonstrated that Cmaxand AUC(0-t)of Sul increased with an increasing dose. The mean t1/2values for Cohorts A, B, and C were 16.85, 17.66, and 11.87 h, respectively. No statistically significant differences were observed between men and women for the main pharmacokinetic parameters, with the exception of t1/2in Cohorts B and C. No significant differences were observed in the absorption and bioavailability of Sul between the fed and fasted states (P > 0.05). Four subjects reported mild AEs during the study. No serious AEs were reported. Sul was shown to be safe and well tolerated in healthy Chinese subjects. Pharmacokinetics studies demonstrated that Sul has adequate oral absorption and bioavailability properties.
Central Laboratory, Shanghai Xuhui Central Hospital/Zhongshan-Xuhui Hospital, Fudan University, Shanghai, 200031, China.
Qian
Q
Chen
Central Laboratory, Shanghai Xuhui Central Hospital/Zhongshan-Xuhui Hospital, Fudan University, Shanghai, 200031, China.
Hong-Jie
HJ
Qian
Department of Emergency, Shanghai Xuhui Central Hospital/Zhongshan-Xuhui Hospital, Fudan University, Shanghai, 200031, China.
Wei
W
Wang
Central Laboratory, Shanghai Xuhui Central Hospital/Zhongshan-Xuhui Hospital, Fudan University, Shanghai, 200031, China.
Meng-Qi
MQ
Zhang
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
Dong-Ying
DY
Lu
Central Laboratory, Shanghai Xuhui Central Hospital/Zhongshan-Xuhui Hospital, Fudan University, Shanghai, 200031, China.
Chuan
C
Lu
Central Laboratory, Shanghai Xuhui Central Hospital/Zhongshan-Xuhui Hospital, Fudan University, Shanghai, 200031, China.
Jie-Mei
JM
Jin
Central Laboratory, Shanghai Xuhui Central Hospital/Zhongshan-Xuhui Hospital, Fudan University, Shanghai, 200031, China.
Chao-Ying
CY
Hu
Central Laboratory, Shanghai Xuhui Central Hospital/Zhongshan-Xuhui Hospital, Fudan University, Shanghai, 200031, China.
Gang-Yi
GY
Liu
Central Laboratory, Shanghai Xuhui Central Hospital/Zhongshan-Xuhui Hospital, Fudan University, Shanghai, 200031, China.
Jing-Ying
JY
Jia
Department of Cardiology, Shanghai Xuhui Central Hospital/Zhongshan-Xuhui Hospital, Fudan University, Shanghai, 200031, China.
Hong-Chao
HC
Zheng
Department of Clinical Pharmacology, Zhong Shan Hospital, Fudan University, Shanghai, 200032, China.
Xue-Ning
XN
Li
Central Laboratory, Shanghai Xuhui Central Hospital/Zhongshan-Xuhui Hospital, Fudan University, Shanghai, 200031, China.
Chen
C
Yu
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
Yi-Ping
YP
Wang
Central Laboratory, Shanghai Xuhui Central Hospital/Zhongshan-Xuhui Hospital, Fudan University, Shanghai, 200031, China.
Yun
Y
Liu
D000293:Adolescent; D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood*; D019540:Area Under Curve; D002681:China; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D064368:Healthy Volunteers; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D013463:Sulfuric Acid Esters / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood*; D055815:Young Adult
D000889:Anti-Arrhythmia Agents; D013463:Sulfuric Acid Esters; C558473:sulcardine sulfate
arrhythmia; pharmacokinetics; sulcardine sulfate; tolerability