中文摘要：

目的:研究胡椒碱对小鼠体内去甲替林药代动力学及脑血分布的影响,为胡椒碱对P-糖蛋白(P-gp)调节作用的研究提供依据。方法:216只小鼠随机分为4组,分别连续服用生理盐水、维拉帕米或不同剂量胡椒碱8 d,并于第8天给予以上药物1 h后腹腔注射去甲替林,于给药后5,15,30 min和1,2,4,6,8,12 h采集血及脑组织,并采用LC-MS/MS法测定去甲替林的浓度,计算血、脑中主要药代动力学参数和脑血浓度比值。结果:与生理盐水组相比,胡椒碱组血和脑组织中去甲替林浓度变化很小,差异无统计学意义(P】0.05)。低剂量胡椒碱能够使去甲替林的脑血浓度比值及药物浓度-时间曲线下面积(AUC0-12 h)减小,高浓度胡椒碱则无此影响。结论:低剂量胡椒碱可能可以诱导血脑屏障上P-gp的活性,而高剂量胡椒碱对血脑屏障上P-gp无此作用。

英文摘要：

Objective: To study the pharmacokinetics and brain/plasma concentration ratio of nortriptyline at multiple doses in mice which were pre-treated with physiological saline, piperine and verapamil. Methods: A total of 216 male Kun Ming mice[(25±3) g] were equally divided into 4 groups randomly. Each group was intragastrically administered physiological saline (B), piperine (170 μg/kg), piperine (5 mg/kg) and verapamil (5 mg/kg) for 8 days. On the 8th day, 1 h atfer giving the above drugs, each mice was intraperitoneally injected nortriptyline (13 mg/kg). The mice were sacriifced by picking off eyeballs at the time intervals of 5, 15, 30 min, and 1, 2, 4, 6, 8 and 12 h, andthe cerebra were collected and weighted. Nortriptyline in mouse plasma and brain was determined by HPLC-MS/MS. The pharmacokinetic properties of the plasma, brain and brain/plasma were calculated. Results: hTe AUC0-12 h of brain/plasma concentration ratio in the 170 μg/kg piperine group was significantly lower than that in the other groups (P<0.05), while the AUC0-12 h of brain/plasma concentration ratios in the 5 mg/kg piperine group and the verapamil group were not signiifcantly different from those of untreated mice. Conclusion: Piperine (170 μg/kg) may induce P-glycoprotein expression in the blood-brain barrier, while piperines at 5 mg/kg has no influence on P-glycoprotein expression in the blood-brain barrier.