艾司西酞普兰在健康人体的药动学

目的:评价健康中国人口服艾司西酞普兰片后的药动学。方法:20名健康受试者男女各半,分别进行艾司西酞普兰片低(5mg)、中(10mg)、高(20mg)3种剂量水平的单剂量药动学试验,并对中间剂量进行多次给药及稳态试验。采用高效液相色谱-串联质谱(HPLC-MS/MS)法测定血浆艾司西酞普兰浓度,用DAS软件进行数据处理。结果:单剂量口服5、10和20 mg艾司西酞普兰后,主要药动学参数AUC_(0～144)分别为(219±s 49),(367±60)和(689±174)μg·h·L~(-1);AUC_(0～∞)分别为(242±64),(414±79)和(745±207)μg·h·L~(-1);c_(max)分别为(5.5±1.0),(8.8±1.3)和(21±6)μg·L~(-1);t_(max)分别为(4±3),(6±3)和(3.0±1.5)h;t_(1/2)分别为(40±11),(48±10)和(37±6)h;MRT分别为(56±13),(63±11)和(51±7)h。多剂量口服10 mg艾司西酞普兰受试制剂后,艾司西酞普兰的主要药动学参数AUC_(0～144)为(914±202)μg·h·L~(-1);AUC_(0～∞)为(993±214)μg·h·L~(-1);AUC_(ss)为(364±78)μg·h·L~(-1);c_(max)~(ss)为(26±4)μg·L~(-1);c(min)~(ss)为(12.4±1.1)μg·L~(-1);c_(av)~(ss)为(15±3)μg·L~(-1);DF为0.87±0.22;t_(max)为(2.6±1.7)h;t_(1/2)为(40±7)h。结论:艾司西酞普兰的体内过程符合二房室开放模型,在研究剂量范围(5～20 mg)内c_(max)和AUC的增加与剂量呈正相关,t_(max)、t_(1/2)和MRT基本不受剂量变化的影响,具线性药动学行为。

Pharmacokinetics of escitalopram in healthy volunteers

AIM:To study the pharmacokinetics of escitalopram in healthy Chinese volunteers.METHODS: The volunteers were given a single oral dose of 5,10 or 20 mg escitalopram for single dose pharmacokinetics, or 10 mg escitalopram tablets once a day for 10-days multidose and steady-state study.The plasma concentrations of escitalopram were determined by a validated HPLC-MS/MS method.The pharmacokinetic parameters were calculated by DAS 2.0 software.RESULTS:The main pharmacokinetic parameters of escitalopram after the single oral dose of 5,10 or 20 mg were as follows:AUC_(0-144) were (219±s 49),(367±60) and (689±174)μg·h·L~(-1),respectively;AUC_(0-∞) (242±64),(414±79) and (745±207)μg·h·L~(-1);c_(max) (5.5±1.0), (8.8±1.3) and (21±6)μg·L~(-1);t_(max) (4±3),(6±3) and (3.0±1.5) h;t_(1/2) (40±11),(48±10) and (37±6) h;MRT (56±13),(63±11) and (51±7) h.The parameters after multidose of 10 mg were as follows:AUC_(0-144) was (914±202)μg·h·L~(-1),AUC_(0-∞) (993±214)μg·h·L~(-1),AUC_(ss) (364±78)μg·h·L~(-1), c_(max)~(ss)(26±4)μg·L~(-1),c_(min)~(ss)(12.4±1.1)μg·L~(-1),c_(av)~(ss)(15±3)μg·L~(-1),DF 0.87±0.22,t_(max) (2.6±1.7) h,t_(1/2) (40±7) h.CONCLUSION:The plasma concentration-time curve of escitalopram is fitted with a two- compartment open pharmacokinetic model.The c_(max) and AUC are proportional with the dose ranged from 5 to 20 mg,respectively,while the t_(max),t_(1/2),and MRT are not affected by the dose.Therefore,the linear pharmacokinetics of escitalopram in human plasma is found in Chinese healthy volunteers.