氟西汀及其活性代谢产物在汉族健康人体的药动学  

Pharmacokinetic study of fluoxetine and its active metabolite in healthy Han Chinese volunteers

作　　者：师少军[1] 刘亚妮[1] 李忠芳[1] 陈笑艳[2] 曾繁典[3] 

机构地区：[1]华中科技大学同济医学院附属协和医院,湖北武汉430022 [2]中国科学院上海药物研究所药物代谢研究中心,上海201203 [3]华中科技大学同济医学院临床药理研究所,湖北武汉430030

出　　处：《中国医院药学杂志》2011年第20期1686-1689,共4页Chinese Journal of Hospital Pharmacy

基　　金：湖北省自然科学基金(编号:2009CDB380)

摘　　要：目的:探讨氟西汀及其活性代谢产物去甲氟西汀在汉族健康人体的药动学。方法:24名健康男性志愿者单剂量口服盐酸氟西汀分散片20 mg后,采用液相色谱-串联质谱法测定血浆中氟西汀和去甲氟西汀浓度,应用DAS2.0软件计算药动学参数。结果:氟西汀和去甲氟西汀在人体内药-时曲线呈一室模型。除1例慢代谢型受试者外,23名受试者主要药动学参数如下:t1/2分别为(30.8±7.6)和(130.9±42.0)h;tmax分别为(5.5±2.1)和(58.5±31.7)h;Cmax分别为(11.8±3.5)和(14.2±5.0)ng.mL-1;AUC0-t分别为(487.4±190.2)和(3370.9±1175.8)ng.h.mL-1;AUC0-∞分别为(506.5±208.8)和(3537.8±1424.1)ng.h.mL-1。结论:盐酸氟西汀分散片在人体吸收迅速,消除较慢,而其活性代谢产物去甲氟西汀消除更慢;其中1例受试者呈明显慢代谢型。OBJECTIVE To investigate the pharmacokinetics of fluoxetine and its active metabolite norfluoxetine in healthy Han Chinese volunteers. METHODS A single oral dose of 20 mg fluoxetine hydrochloride dispersible tablets were given to 24 male healthy volunteers. The concentrations of fluoxetine and norfluoxetine in plasma were measured using a validated liquid chromatography with the tandem mass spectrometer detection （LC-MS/MS） method. The pharmacokinetic parameters were calculated with DAS ver2. 0 program. RESULTS The concentration-time curves of fluoxetine and norfluoxetine were fitted to a one-compartment open model. Except for one poor metabolizer, the main pharmacokinetic parameters were as follows： 6/2 were （30.8±7.6） and （130.9±42.0）h; tmax were （5.5±2. 1） and （58. 5 ± 31. 7）h; Cmax were （11.8±3.5） and （14.2± 5.0）ng. mL-1 ; AUC0-1 were （487. 4 ± 190. 2） and （3370. 9 ± 1175.8） ng· h· mL^-1 ; AUC0-∞ were （506. 5 ± 208. 8） and （3537. 8 ± 1424. 1）ng· h· mL^-1, respectively. CONCLUSION Fluoxetine hydrochloride dispersible tablet is absorbed rapidly and eliminated slowly. Norfluoxetine is eliminated much more slowly than its parent drug. One poor mctabolizer is found in these healthy volunteers.

关 键 词：氟西汀 去甲氟西汀 液相色谱-串联质谱法 药动学 

分 类 号：R969.1[医药卫生—药理学]