中国健康男性受试者单次口服盐酸伊伐布雷定前后心率与血药浓度的变化  

Pharmacokinetics of single oral dose of ivabradine hydrochloride and effect on heart rate in healthy male volunteers

作　　者：许莉 蒋娟娟 谢爽 娄莹 王莉[1] 庞会敏 田蕾 李一石 

机构地区：[1]中国医学科学院北京协和医院阜外心血管病医院卫生部心血管药物临床研究重点实验室,北京100037

出　　处：《中国新药杂志》2013年第15期1789-1792,1796,共5页Chinese Journal of New Drugs

基　　金：国家"重大新药创制"科技重大专项(2012ZX09303008-001);国家临床重点专科建设项目--<卫生部重点实验室项目>

摘　　要：目的:评价中国健康受试者单次口服盐酸伊伐布雷定后血药浓度的变化及对心率的影响。方法:36例受试者随机分为3组,分别单次口服伊伐布雷定5,10,20 mg(每组n=12),在规定的时间内采集血样(药前,药后0.25,0.5,0.75,1,1.5,2,4,6,8,12,24 h)和测量心率(药前,药后2,6,12,24 h)。采用HPLC-MS/MS法测定血浆中的盐酸伊伐布雷定浓度。结果:受试者单次口服盐酸伊伐布雷定5,10,20 mg后,达峰浓度Cmax分别为(9.67±4.55),(23.1±13.0),(46.9±18.5)ng.mL-1,达峰时间Tmax分别为(1.0±0.5),(1.0±0.4)和(0.9±0.5)h。单次服药后2 h,受试者的心率分别下降(5.27±10.96)%,(5.86±12.50)%,(10.17±8.90)%,药后6 h心率基本恢复至药前水平。3组受试者药后45 min～1 h血浆伊伐布雷定的浓度最高,药后2 h心率的下降幅度最大,即最大药物浓度和最大药效之间有时间差。结论:盐酸伊伐布雷定能够降低中国健康男性受试者的静息心率,心率下降幅度具有剂量依赖性。Objective：To investigated the pharmacokinetics of single oral dose of ivabradine hydrochloride and evaluate its effect on heart rate in healthy male Chinese volunteers. Methods：Thirty-six volunteers were ran- domized to 3 groups： ivabradine 5 mg（n = 12） ,10 mg（n = 12） ,and 20 mg（n = 12）. Blood samples were collected at 0.25, 0.5, 0.75, 1 , 1.5, 2, 4, 6, 8, 12, and 24 h, and heart rates were recorded at 2, 6, 12, and 24 h after single dose administration of ivabradine. The plasma concentrations of invabradine were determined by HPLC-MS/ MS method. Results：After single dose administration, the Cmax was （9.67±4.55）, （23.1± 13.0）, and （46. 9 ± 18.5） ng mL-I for 5, 10, and 20 mg hydrochloride ivabradine respectively, Tmax was （ 1.0 ± 0.5 ）, （ 1.0 -± 0.4） , and （0.9 ±0.5） h respectively. Resting heart rate was reduced at 2 h and returned to baseline at 6 h. The maxi- mum decrease percentage of heart rate was （5.27 ±10.96） % , （5.86 ±12.50） % , and （10.17 ±8.90）% , re- spectively. There was a significant lag time between peak plasma concentration of ivabradine and maximum brady- cardic effect. The peak plasma concentration of ivabradine appeared at 45 min to 1 h after administration, while the maximum decrease of Chinese male healthy volunteer resting heart rate in a dose-dependent effect.

关 键 词：盐酸伊伐布雷定 血药浓度 心率 

分 类 号：R972[医药卫生—药品]