注射用磷丙泊酚钠在Ⅰ期临床耐受性试验中对健康受试者QT间期的影响  

Effect of Single Doses of HX0507 on QTc Intervals in Healthy People: a Phase Ⅰ Safety and Tolerability Study

作　　者：伊晓倩[1,2] 李蕊[1] 张文胜[1] 刘进[1] 徐晶[1] 廖天治[3] 

机构地区：[1]四川大学华西医院转化神经科学中心麻醉与危重急救研究室,成都610041 [2]山东中医药大学附属医院 [3]四川大学华西医院重症医学科,成都610041

出　　处：《四川大学学报（医学版）》2012年第6期868-872,共5页Journal of Sichuan University(Medical Sciences)

摘　　要：目的探讨注射用磷丙泊酚钠(HX0507)在Ⅰ期临床耐受性试验中对健康受试者心电图QT间期的影响,了解其临床应用可能存在的风险。方法将80例健康受试者顺序分配到13个剂量组。给药前记录基础心电图,并于给药后24h内33个时点记录心电图。求得使用Fridericia公式和Bazett公式校正的QT间期,即QTcF(QTcF=QT/RR0.33)与QTcB(QTcB=QT/RR0.5)。以QTcF与基线值的差值(ΔQTcF)为主要目标变量分析HX0507对健康受试者QT间期的影响。结果注射用磷丙泊酚钠在可能的临床常用剂量(3mg/kg)和更大剂量(8～40mg/kg)组给药后ΔQTcF均值在5.61～32.24ms间,双侧90%可信区间上限在10.30～53.90ms间。32例受试者出现了8种心电图相关的不良反应。结论注射用磷丙泊酚钠在3mg/kg和8～40mg/kg剂量组对健康受试者QT间期有剂量相关性延长的趋势。Objective To assess the effect of HX0507 on QTc interval in healthy people in a phase I safety and tolerability study. Methods Eighty healthy people were randomly assigned to one of the 13 dosage groups. Standard 12-lead ECGs data were collected before and after HX0507, a water soluble prodrug of propofol, was given intravenously to the participants （at 33 time points）. The QT interval values were corrected for heart rate using Fridericia＇ s formula （QTcF= QT/RR^0.33 ） and Bazett＇ s formula （QTcB = QT/RR^0.5 ）. The primary target variable was baseline-adjusted changes in QTeF （/XQTcF）. Results Prolongation of QT interval was induced by HX0507 administered at an anticipated clinical dosage （3 mg/kg） or at a stronger dosage （8 mg/kg ）and above. The mean AQTeF ranged from 5.61 ms to 32.24 ms, with an upper limit of 90% CI ranging from 10.30 ms to 53.90 ms. There was a linear correlation between HX0507 dosage and its effect on QT interval. Eight types of ECG-related adverse events were detected in 32 subjects. Conclusion Single administration of HX0507 induces dose-related QT prolongation.

关 键 词：注射用磷丙泊酚钠 QT间期 Ⅰ期临床耐受性试验 

分 类 号：R541.7[医药卫生—心血管疾病]