P-糖蛋白抑制剂维拉帕米对龙血素A、B、C在大鼠体内药物动力学影响  

Effect of P-Glycoprotein Inhibitor Verapamil on Pharmacokinetics of Loureirin A B C in Rats

作　　者：李玉娟[1] 康丽婷 郭晶晶 王识博 李勇枝[2] 王佳平[2] 高建义[2] LI Yu-juan;KANG Li-ting;GUO Jing-jing;WANG Shi-bo;LI Yong-zhi;WANG Jia-ping;GAO Jian-yi(School of Life Science,Beijing Institute of Technology,Beijing 100081,China;China Astronaut Research and Training Centre,Beijing 100094,China)

机构地区：[1]北京理工大学生命学院,北京100081 [2]中国航天员科研训练中心,北京100094

出　　处：《北京理工大学学报》2020年第1期105-110,共6页Transactions of Beijing Institute of Technology

基　　金：国家自然科学基金资助项目(81573693);“1226”重大项目(AWS16J018)

摘　　要：研究灌胃给予大鼠龙血竭后,P糖蛋白抑制剂维拉帕米对其有效成分龙血素A、B、C在大鼠血浆中的药物动力学影响.将SD大鼠随机分为对照组和抑制剂组并单次给药,对照组灌胃给予大鼠5 g/kg龙血竭,抑制剂组联合给予大鼠维拉帕米(1 mg/kg)和龙血竭(5 g/kg).收集两组相同系列时间的血浆样本,采用HPLC-MS/MS的方法对龙血素A、B、C在大鼠血浆中的浓度测进行检测,求算两组血浆样本药物动力学参数.与对照组相比,抑制剂组大鼠龙血素A、B、C的血药浓度时间曲线下面积分别增加109.4%,78.5%,22.8%,血药峰浓度分别增加69.6%,115.0%,42.1%,龙血素A、B的达峰时间均延长、龙血素C的达峰时间无变化,三者的生物半衰期(T 0.5)均变小,说明P糖蛋白抑制剂能够引起龙血素A、B、C在大鼠体内的血浆药物动力学参数变化,龙血素A、B、C均有可能为P糖蛋白的潜在底物.To study how P-glycoprotein inhibitor verapamil affect pharmacokinetics of the active constituents Loureirin A,B and C in rat plasma after oral administration of Dragon’s Blood,SD rats were randomly put into different group:control group and inhibitor group.A single dose of 5 g/kg of Dragon’s Blood was orally administered to rats in control group,and rats in the inhibitor group were given verapamil(1 mg/kg)and Dragon’Blood(5 g/kg).Plasma samples were collected from the two groups in the same series of time.A HPLC-MS/MS method was used to determine the content of Loureirin A,B and C in rat plasma,and the plasma samples pharmacokinetic parameters were calculated.Comparing the area under curve(AUC0-t)of the rats in the inhibitor group with the control group,it increased by 109.4%,78.5%,22.8%.And the peak concentration(C max)of Loureirin A,B and C increased by 69.6%,115.0%,and 42.1%.The time of Loureirin A and B reaching peak concentration(t max)was prolonged,while the t max of Loureirin C was unchanged.All three biological half-life(t 0.5)decreased.It indicates that P-glycoprotein inhibitor can significantly change the plasma pharmacokinetic parameters of Loureirin A,B and C in rats.Loureirin A,B and C may be potential substrates of P-glycoprotein.This article provides basic data for the subsequent in-depth study of the relationship between P-glycoprotein and transportation of Dragon’s Blood in the intestinal tract of rats.

关 键 词：P糖蛋白 龙血竭 药物动力学 维拉帕米 

分 类 号：R917[医药卫生—药物分析学]