伊伐布雷定人体药动学研究

目的评价伊伐布雷定在中国人群中药代动力学特性。方法将30名健康受试者随机平均分为3组,分别给予2.5、5、7.5 mg伊伐布雷定片,给药后8、15、30、45 min和1、1.5、2、3、4、6、9、12、24、36、48 h分别采集静脉血,并用HPLC-MS/MS法进行血药浓度检测。结果单次口服盐酸伊伐布雷定片后,血浆中伊伐布雷定的t1/2为(4.4±1.0)、(5.2±1.2)、(4.6±1.2)h;C max为(15.1±4.1)、(35.9±8.9)、(48.2±9.6)ng·ml-1;AUC(0～48)为(64.4±14.2)、(169.6±33.1)、(215.6±55.6)ng·h·ml-1;去甲伊伐布雷定的t1/2为(7.9±1.4)、(9.9±1.2、(9.8±1.3)h;C max为(1.8±0.7)、(3.1±1.6)、(6.3±1.0)ng·ml-1;AUC(0～48)为(13.4±2.8)、(23.9±9.4)、(44.1±9.2)ng·h·ml-1。结论 2.5～7.5 mg伊伐布雷定片在中国人群体内代谢呈线性动力学。

Pharmacokinetics of Ivabradine in Humans

Objective To study the pharmacokinetics of ivabradine in healthy Chinese volunteers.Methods 30 healthy volunteers were randomly divided into 3 groups.They received orally ivabradine(a single dose of 2.5,5 or 7.5 mg,respectively).Blood was collected at 8,15,30,45 min,and 1,1.5,2,3,4,6,9,12,24,36,48 h after drug administration.The concentration of ivabradine and N-desmethylivabradine in human plasma was then determined by HPLC-MS/MS.Results The pharmacokinetic parameters of different doses of ivabradine tablets were: t1/2(4.4±1.0),(5.2±1.2),(4.6±1.2) h;Cmax(15.1±4.1),(35.9±8.9),(48.2±9.6) ng · ml-1;AUC(0-48)(64.4±14.2),(169.6±33.1),(215.6±55.6) ng·h · ml-1 for ivabradine,respectively,and t1/2(7.9±1.4),(9.9±1.2),(9.8±1.3) h;Cmax(1.8±0.7),(3.1±1.6),(6.3±1.0) ng · ml-1;AUC(0-48)(13.4±2.8),(23.9±9.4),(44.1±9.2) ng·h · ml-1 for N-desmethylivabradine,respectively.Conclusion The pharmacokinetic character ivabradine tablets was linear within the range of 2.5 to 7.5 mg in healthy Chinese volunteers.