盐酸度洛西汀肠溶胶囊在中国健康人体内的药动学研究  

Pharmacokinetics of Duloxetine Enteric-Capsules in Healthy Chinese Volunteers

作　　者：张毕奎[1] 徐萍[2] 朱运贵[2] 向大雄[2] 陈本美[3] 冯胜[2] 宋娟[4] 谢志红[4] 马宁[4] 李焕德[2] 

机构地区：[1]中南大学湘雅三医院药剂科,长沙410013 [2]中南大学药学院,长沙410013 [3]中南大学现代分析测试中心生物分析化学研究室,长沙410009 [4]中南大学湘雅二医院临床药学研究室,长沙410011

出　　处：《中国药学杂志》2008年第7期527-531,共5页Chinese Pharmaceutical Journal

摘　　要：目的研究盐酸度洛西汀肠溶胶囊的药动学,为该药的临床应用提供依据。方法分单剂量组和多剂量组进行试验。单剂量组分周期交叉口服高、中、低剂量受试药物,多剂量组按临床常规剂量连续给药7d。采用HPLC-MS测定血浆中度洛西汀的浓度,用DAS2.0对血药浓度-时间数据进行药动学模型拟合和参数计算。结果体内药动学符合一室模型特征。主要药动学参数ρmax,AUC0-72,AUC0-∞与剂量相关,tmax,t1/2则与剂量无关。连续口服盐酸度洛西汀肠溶胶囊,4d后血药浓度达到稳态。除单剂量组口服44.8mg时的Ka值外,主要药动学参数性别间均没有差异。结论盐酸度洛西汀在健康人体内符合线性药动学特征,主要药动学参数没有性别差异。OBJECTIVE To determine the pharmacokinetics of duloxetine and to provide evidence for its clinical application.METHODS The experiment consisted of 2 groups：a single-dose group and a multi-dose group.High,middle and low doses were given orally to each volunteer in turns during different periods in the single-dose group.A clinical routine dose was given to each volunteer in the multi-dose group for 7 d continuously.The plasma concentration of duloxetine was determined by HPLC-MS.Then DAS 2.0 software package was used to fit the plasma concentration-time data and to calculate the parameters.RESULTS The pharmacokinetic profiles were discribed by an one-compartment model.ρmax,AUC0-72,and AUC0-∞ were correlated to the doses,but no tmax and t1/2.Steady state concentration was reached 4 d after the continuous oral administration of duloxetine enteric-capsules.Except for the Ka value after the single oral dose of 44.8 mg duloxetine,there was no gender difference in other pharmacokinetic parameters.CONCLUSION Duloxetine was linearly correlated to the doses in the plasma of healthy volunteers and no gender difference was found in the main pharmacokinetic parameters.

关 键 词：度洛西汀 肠溶胶囊 药动学 高效液相色谱-质谱联用 

分 类 号：R969.1[医药卫生—药理学]