健康人单次口服不同剂量依地普仑片的药动学

Pharmacokinetics of escitalopram in Chinese healthy volunteers after oral administration of different doses

目的:研究中国健康志愿者单次口服不同剂量依地普仑草酸盐片的体内药动学特点。方法:32例受试者单次空腹口服依地普仑草酸盐片,剂量分别为10(n=10),20(n=12),30 mg(n=10)。用HPLC荧光检测法测定血浆中的依地普仑浓度,用DAS统计软件进行数据处理,计算药动学参数。结果:草酸依地普仑片药动学特点符合二房室模型,为线性药动学特点,单次口服依地普仑10,20和30 mg的主要药动学参数是:C_(max)分别为(20.91±4.94),(40.28±10.13)和(57.66±10.51)μg·L^(-1);T_(max)分别为(3.80±1.23),(4.18±0.98)和(4.00±1.49)h;t_(1/2)分别为(34.08±26.58),(36.02±23.68)和(36.95±11.58)h;AUC_(0～t)分别为(846.8±466.7),(1437.5±535.5)和(2277.5±506.5)μg·h·L^(-1),AUC_(0～∞)分别为(975.7±622.4),(1587.1±731.2)和(2496.6±707.4)μg·h·L^(-1)。药动学参数的个体间差异较大,CV%最大值为77.99%。女性受试者和男性受试者的血浆清除率(CL/F)及单位剂量的AUC_(0～t)和AUC_(0～∞)值相似。结论:中国健康受试者单次口服不同剂量草酸依地普仑的药动学参数具有线性药动学特点。

Objective：To explore the pharmacokinetics of escitalopram tablets after single oral administration of different doses in healthy Chinese volunteers. Methods： A total of 32 subjects participated in the study. Escitalopram 10 mg, 20 mg and 30 mg were given orally to 10, 12 and 10 volunteers, respectively. Sequential blood samples were collected and escitalopram concentrations in plasma were determined by a validated high performance liquid chromatography with fluorescence detection. The pharmacokinetic parameters were calculated with DAS software. Resuits：Escitalopram disposition in oral administration was characterized by a two-compartment pharmacokinetic and linear model. The main pharmacokinetic parameters after single doses of 10 mg, 20 mg and 30 mg of escitalopram were： Cmax（20.91±4.94）, （40.28 ±10. 13）,and （57.66 ± 10.51）μg·L^-1; Tmax（3.80 ±1.23）, （4.18 ±0.98） ,and （4.00 ±1.49）h; t1/2（34.08 ±26.58）, （36.02±23.68） and （36.95±11.58） h; AUC0-t （846.8±466. 7）, （1 437. 5 ±535. 5）,and （2 277. 5 ±506. 5）μg·L^-1; AUC0-∞ （975. 7 ±622.4）, （ 1 587.1± 731.2） and （ 2 496.6± 707.4 ）μg·L^-1, respectively. Individual variability was relatively large. The largest CV% value is 77.99%. The CL/F, AUC0-t and AUC0-∞ on single dose were not significantly different （P 〉 0.05） between male and female subjects. Conclusion： Escitalopram pharmacokinetics in healthy Chinese subjects at three different doses is characteristic of linear pharmacokinetics.