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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。
Objective: To study the pharmacokinetics of duloxetine hydrochloride enteric-coated tablets in healthy volunteers. Methods: LC-MS / MS was used to determine the pharmacokinetic parameters of single-dose and multi-dose oral duloxetine hydrochloride enteric-coated tablets in healthy volunteers. Results: The healthy volunteers were given 30,60,90 mg duloxetine hydrochloride enteric-coated tablets in a single dose, with Cmax of (22.5 ± 15.2), (44.4 ± 17.2), (60.8 ± 27.8) μg · L -1, AUC0-60 (359.7 ± 201.0), (733.8 ± 343.4), (1280.5 ± 644.81) μg.hL-1 were significantly higher than that of the control group (328.6 ± 203.6), (696.0 ± 337.8) and (1219.3 ± 598.3) , tmax was (6.8 ± 2.0), (6.1 ± 1.3), (6.6 ± 1.6) h, t1 / 2 was (13.0 ± 3.6), (12.8 ± 2.3) and (11.7 ± 2.1) h respectively. Cmax, AUC0-60, AUC0-∞ in the dose of 30 ~ 90mg administered dose was linear. Statistical analysis showed that tmax, t1 / 2 in the above-mentioned different dose groups showed no significant difference (P> 0.05). After 3 days of continuous administration, the plasma concentration of CsMSax was (47.3 ± 17.0) μg · L-1, and the Csmsin was (27.9 ± 9.5) μg · L-1. The AUC (ss0- 12) was (407.25.6 ± 125.9) μg.hL-1. CONCLUSION: The in vivo absorption of duloxetine hydrochloride enteric-coated tablets (Cmax, AUC0-60) has a linear kinetic profile within the dose range of 30-90 mg.