盐酸托莫西汀胶囊在健康人体药动学探究.docVIP

盐酸托莫西汀胶囊在健康人体药动学探究 　 作者：饶斯清，陈楚雄，杨梦心，温预关【摘要】 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。 【关键词】 盐酸托莫西汀胶囊;高效液相色谱串联质谱法;药动学 　　Abstract: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. 　　Key words:atomoxetine hydrochloride capsules;HPLC/MS/MS;pharmacokinetics 　 托莫西汀(atomoxetine，商品名：择思达)是第1个用于治疗注意缺陷多动障碍(attention deficit hyperactivity disorder，ADHD)的非兴奋性药物，目前已经在美国、英国、中国等多个国家上市并应用[1]。托莫西汀是一种去甲肾上腺素再摄取抑制剂，能选择性抑制突触前胺泵对去甲肾上腺素的再摄取，增强去甲肾上腺素的翻转效应，从而改善多动症的症状，间接促进认知的完成和注意力的集中[2,3]。有关托莫西汀的药动学研究，