【摘要】 目的:研究盐酸度洛西汀肠溶片在健康人体内的药动学。方法:采用液相色谱-串联质谱法(LC-MS/MS)测定健康志愿者单剂量和多剂量口服盐酸度洛西汀肠溶片后的血药浓度,计算药动学参数。结果:健康志愿者单剂量口服30,60,90mg盐酸度洛西汀肠溶片,Cmax为(22.5±15.2),(44.4±17.2),(60.8±27.8)μg·L-1,AUC0-60为(328.6±203.6),(696.0±337.8),(1219.3±598.3)μg.h.L-1,AUC0-∞为(359.7±201.0),(733.8±343.4),(1280.5±644.81)μg.h.L-1,tmax为(6.8±2.0),(6.1±1.3),(6.6±1.6)h,t1/2为(13.0±3.6),(12.8±2.3),(11.7±2.1)h。Cmax、AUC0-60、AUC0-∞在30～90mg内与给药剂量呈线性关系。统计分析结果表明tmax、t1/2在上述不同剂量组之间差异无显著性(P>0.05)。受试者连续给药3d后血药浓度达稳态,达到稳态后的Csmsax为(47.3±17.0)μg·L-1,Csmsin为(27.9±9.5)μg·L-1,AUC(ss0-12)为(407.25.6±125.9)μg.h.L-1。结论:盐酸度洛西汀肠溶片体内吸收程度(Cmax、AUC0-60)在30～90mg给药剂量内具有线性动力学特征。更多还原

【Abstract】 OBJECTIVE To study the pharmacokinetics of duloxetine hydrochloride enteric-coated tablets in healthy volunteers.METHODS Determine the concentration of duloxetine in plasma after the volunteers’ administration of a single dose or multiple doses of duloxetine by liquid chromatography-tandem mass spectrometry (LC-MS/MS).RESULTS After the healthy volunteers received a single dose of 30,60,90 mg duloxetine,the main pharmacokinetics parameters were as follows:Cmax were (22.5±15.2) ,(44.4±17.2),(60.8±27.8) μg·L-1; AUC0-60 were (328.6±203.6),(696.0±337.8),(1 219.3±598.3) μg·h·L-1 AUC0-∞ were (359.7±201.0),(733.8±343.4),(1 280.5±644.8) μg·h·L-1; tmax were (6.8±2.0)、(6.1±1.3)(6.6±1.6)h; t1/2 were(13.0±3.6),(12.8±2.3),(11.7±2.1)h.In the dose of 30-90 mg there was a significantly dependability between Cmax、AUC0-60、AUC0-∞ and dosage.The statistical result showed that tmax、t1/2 had no significant difference(P>0.05) in three groups.Steady state was achieved after 3 day consecutive administration.Cssmax was(47.3±17.0)μg·L-1,Cssmin was(27.9±9.5)μg·L-1,AUCss(0-12) was (407.25.6±125.9) μg·h·L-1.CONCLUSION The dynamics of duloxetine hydrochloride enteric-coated tablets in vivo are linear in the dosage of 30-90 mg.更多还原