HPLC-MS法测定血浆中的帕罗西汀及人体内药动学研究

Study on the pharmacokinetics of paroxetine hydrochloride tablets in healthy volunteers with HPLC-MS assay

目的 研究盐酸帕罗西汀的血浆浓度测定方法及其在人体内的药动学。方法 18名健康男性志愿者 ,单剂量口服盐酸帕罗西汀片 ,在设计的时间点取静脉血 ,血药浓度采用液相色谱 质谱 (HPLC MS)法测定。药动学参数采用 3P97程序计算。结果 单次服用 4 0mg盐酸帕罗西汀片后的主要药动学参数Ka ,AUC0～ 96,AUC0～∞ ,cmax,tmax,CL分别为 ( 0 .89± 0 .2 8)h-1,( 5 76 .2± 2 36 .0 )ng·h·mL-1,( 5 96 .8± 2 34.5 )ng·h·mL-1,( 2 6 .3± 9.6 )ng·mL-1,( 3.89± 2 .1)h ,( 0 .0 9± 0 .0 5 )L·h-1。结论 盐酸帕罗西汀片在中国人体内口服吸收缓慢 ,约 4h达到血药浓度峰值 ,平均消除半衰期为 19～ 2

OBJECTIVE: To study the pharmacokinetics of paroxetine hydrochloride tablets in healthy volunteers with HPLC-MS. METHODS: A single oral dose of 40 mg paroxetine hydrochloride was given to 18 healthy volunteers. The concentrations of paroxetine in plasma were assayed by HPLC-MS method. The pharmacokinetic parameters of paroxetine hydrochloride tablets were calculated by program 3P97. RESULTS: The pharmacokinetic parameters of paroxetine hydrochloride tablets were as follows: Ka (0.89 ± 0.28) h -1,AUC0∼96(576.2±236.0) ng&middoth&middot mL-1,AUC0∼∞(596.8±234.5) ng&middoth&middotmL-1,cmax(26.3±9.6) ng&middotmL-1, tmax(3.89 ±2.1) h,CL(0.09+0.05) L&middoth-1 respectively. CONCLUSIONS: Paroxetine hydrochloride tablet was absorbed slowly in healthy volunteers. Its peak blood concentration was reached at 4 h after oral administration with t1/2 19∼23 h.