盐酸度洛西汀对他林洛尔人体药物动力学的影响  

Effect of duloxetine on the pharmacokinetics of talinolol in humans

作　　者：赵瑞柯 曹俊华 刘保川 谭晓安 彭文兴[2] 

机构地区：[1]长沙市八医院,长沙410000 [2]中南大学湘雅二医院临床药学教研室,长沙410011

出　　处：《中南药学》2011年第6期430-433,共4页Central South Pharmacy

摘　　要：目的通过考察盐酸度洛西汀对P糖蛋白底物——他林洛尔药物动力学的影响,探讨盐酸度洛西汀对P-糖蛋白的作用。方法采用随机开放,两周期自身前后对照试验设计,12名健康受试者第1周期单剂量口服他林洛尔1片（50 mg）,第2周期受试者服用度洛西汀（30 mg.次-1,2次.d-1）,连续服用6 d,于第7日晨加服他林洛尔1片（50 mg）。采用高效液相色谱-串联质谱检测血样药物浓度,计算并比较药物动力学参数。结果受试者多剂量服用盐酸度洛西汀后,他林洛尔的AUC0-60和Cmax由单用时的1 348.54、91.90 ng.mL-1分别增加至1 498.30和125.21 ng.mL-1。AUC和Cmax分别增加了11%和36%。等效性分析显示2周期AUC和Cmax比值的90%置信区间分别为77%~106%和68%~112%,均落于等效范围之外。他林洛尔的其他药动学参数tmax,t1/2,CL/F,V/F在2周期间并无显著性差异。结论盐酸度洛西汀增加了他林洛尔的生物利用度,可能的原因是盐酸度洛西汀抑制了肠道P-糖蛋白的功能,增加了其吸收程度。Objective To evaluate the effect of duloxetine on P-glycoprotein function by determining the effect of orally administered duloxetine on the pharmacokinetics of talinolol in humans.Methods A self-controlled 2-period experiment was conducted with a randomized,openlabeled design in 12 healthy volunteers.In the 1st period,the volunteers received a single oral dose of 50 mg talinolol.After the 1-week washout,the volunteers received 30 mg duloxetine twice daily for 6 d.On the 7th day,they received 30 mg duloxetine and 50 mg talinolol concomitantly.The concentration of talinolol was determined by HPLC-ESI-MS/MS,and the pharmacokinetic parameters of talinolol were calculated and compared.Results After the subjects were treated with duloxetine,the AUC0-60 and Cmax of talinolol increased from 1 348.54 ng·h·mL-1 to 1 498.30 ng·h·mL-1 and 91.90 ng·mL-1 to 125.21 ng·mL-1,respectively.The AUC0-60 and Cmax of talinolol were increased by 11%and 36%,respectively.The 90% CIs for the ratios of AUC（77%-106%） and Cmax（68%-112%） did not fell in the accepted range（80%-125%）.No significant difference in any other pharmacokinetic parameters was observed between the 2 periods（tmax,t1/2,CL/F,and V/F）.Conclusion A 6-day treatment with duloxetine increases the oral bioavailability of talinolol.The increase in oral bioavailability of talinolol can be attributed to the inhibition of P-glycoprotein by duloxetine in the small intestine

关 键 词：度洛西汀 P-糖蛋白 他林洛尔 药物动力学 

分 类 号：R969.1[医药卫生—药理学] R927.1[医药卫生—药学]