盐酸托莫西汀胶囊在健康人体的药动学研究

目的建立快速、灵敏的托莫西汀人体内血药浓度的高效液相色谱串联质谱测定法,并对12名健康志愿者口服盐酸托莫西汀胶囊后在人体内的药动学过程进行研究。方法 12名健康志愿者单剂量口服给药20 mg后,分别于给药前和给药后0.25、0.5、0.75、1、1.5、2、3、4、5、6、8、10、12、24 h采集血样。用高效液相色谱串联质谱法测定血浆中托莫西汀的浓度,并采用DAS药动学程序对试验数据进行处理,求算有关药动学参数。结果单剂量口服给药盐酸托莫西汀胶囊20 mg后,其平均血药质量浓度-时间曲线拟合符合二室模型,T1/2、Tmax、Cmax、AUC0-24、AUC0-∞分别为（4.55±0.79）h、（1.33±0.48）h、（225.18±48.53）μg.L^-1、（971.34±219.52）μg.L^-1.h和（992.60±229.93）μg.L^-1.h。结论建立的托莫西汀人体内血药浓度测定方法灵敏、可靠、简便,盐酸托莫西汀胶囊单剂量给药后在中国健康人体内的药动学行为与国外文献报道基本一致。

Pharmacokinetics of atomoxetine hydrochloride capsules in healthy volunteers

Objective To develop a rapid and sensitive HPLC/MS method for the analysis of atomoxetine in human plasma,and study the pharmacokinetics characteristics of atomoxetine hydrochloride capsules after a single oral dose of 20 mg in healthy volunteers.Methods A single oral dose of 20 mg atomoxetine hydrochloride capsules was given to 12 healthy volunteers.Blood samples were taken for detecting plasma concentration before dosing and at 0.25,0.5,0.75,1,1.5,2,3,4,5,6,8,10,12,24 h after administration.HPLC/MS/MS method was used to assay the concentration of atomoxetine in plasma.The pharmacokinetic parameters were evaluated with DAS program.Results The concentrations of atomoxetine in plasma were fitted with a two-compartment model.The main pharmacokinetic parameters of atomoxetine by oral administration were as follows： T1/2（4.55±0.79）h,Tmax（1.33±0.48）h,Cmax（225.18±48.53）μg·L^-1,AUC0-24（971.34±219.52）μg·L^-1·h,AUC0-∞（992.60±229.93） μg·L^-1·h.Conclusion The analytical method appeared to be accurate,sensitive and convenient,and the pharmacokinetic characteristic of atomoxetine hydrochloride capsules was consistent with the literature data.