CAJ | 학술논문

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。
목적：연구호초감대소서체내거갑체림약대동역학급뇌혈분포적영향，위호초감대P-당단백(P-gp)조절작용적연구제공의거。방법：216지소서수궤분위4조，분별련속복용생리염수、유랍파미혹불동제량호초감8 d，병우제8천급여이상약물1 h후복강주사거갑체림，우급약후5，15，30 min화1，2，4，6，8，12 h채집혈급뇌조직，병채용LC-MS/MS법측정거갑체림적농도，계산혈、뇌중주요약대동역학삼수화뇌혈농도비치。결과：여생리염수조상비，호초감조혈화뇌조직중거갑체림농도변화흔소，차이무통계학의의(P>0.05)。저제량호초감능구사거갑체림적뇌혈농도비치급약물농도-시간곡선하면적(AUC0-12 h)감소，고농도호초감칙무차영향。결론：저제량호초감가능가이유도혈뇌병장상P-gp적활성，이고제량호초감대혈뇌병장상P-gp무차작용。
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.