经典藏药如意珍宝片多次给药的药代动力学研究  

Pharmacokinetics of Classic Tibetan Medicine-ruyi Zhenbao Tablets after Repeated Administration

作　　者：侯红平 王彩霞[1] 彭博 李冰 刘荣霞 陈腾飞 李峰 车向宜 宋玲 高云航 杨庆[1] 罗倩 叶祖光[1] 张广平[1] HOU Hongping;WANG Caixia;PENG Bo;LI Bing;LIU Rongxia;CHEN Tengfei;LI Feng;CHE Xiangyi;SONG Ling;GAO Yunhang;YANG Qing;LUO Qian;YE Zuguang;ZHANG Guangping(Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100029,China;Yantai Saipute Analyzing Service Co.,Ltd,Yantai 264005,China;Yantai University,Yantai 264005,China;Gansu Cheezheng Industrial Group Co.,Ltd.,Beijing 100102,China)

机构地区：[1]中国中医科学院中药研究所,北京100029 [2]烟台赛普特检测服务有限公司,烟台264005 [3]山东烟台大学,烟台264005 [4]甘肃奇正藏药有限公司,北京100102

出　　处：《世界中医药》2024年第4期469-472,480,共5页World Chinese Medicine

基　　金：国家重点研发计划项目(2019YFC1712403)——经典藏药如意珍宝片和白脉软膏治疗藏医重大疾病白脉病的示范开发研究;中央级公益性科研院所基本科研业务费专项基金资助项目(ZZ13-YQ-060,ZXKT21020)——基于PINK1/Parkin介导的线粒体自噬动态平衡在痰热清干预慢阻肺的机制研究。

摘　　要：目的:探讨经典藏药如意珍宝片多次给药的血浆药代动力学特征,为临床用药提供参考和依据。方法:选取斯泼累格·多雷(SD)大鼠12只,雌雄各半,分为对照组和给药组,连续给药7 d,在最后一次给药前0 h及给药开始后0.25、0.5、0.75、1、2、4、8、24、48 h眼眶采血,测定血浆中沉香四醇、异甘草素、胡椒碱、阿魏酸的药代参数。结果:血浆中沉香四醇、异甘草素、胡椒碱、阿魏酸的药代参数达峰时间大部分分别在1~8、0.25、0.25~8、0.25 h;C_(max)分别为(140±53.90)、(8.31±6.34)、(33.4±22.20)、(15.7±7.90)ng/mL;t_(1/2)分别为(10.1±3.85)、(8.51±4.23)、(4.45±1.35)、(67.3±55.10);AUC_(0-t)分别为(1 890±1 440)、(45.6±14.3)、(288±150)、(443±165) h×ng/mL;MRT_(0-∞)分别为(13.2±7.45)、(9.80±4.27)、(4.91±1.34)、(103±77.10) h。沉香四醇、异甘草素、胡椒碱在大鼠体内主要药动学参数差异无统计学意义(P>0.05),阿魏酸在大鼠体内主要药动学参数(C_(max)、AUC_(0-t))差异有统计学意义(P<0.05)。结论:本研究建立了适用于如意珍宝片多次给药后的沉香四醇、异甘草素、胡椒碱、阿魏酸4种成分的药代动力学的研究方法,分析其药代动力学特征,指导临床给药周期和间隔。Objective:To explore the pharmacokinetics characteristics of Ruyi Zhenbao Tablets in the plasma,a classic Tibetan medicine,after repeated administration,so as to provide a reference and basis for clinical application.Methods:Six male and six female SD rats were divided into the control group and the administration group.They were administered for seven days.Blood samples were collected from their eyes at 0 min before the last administration and 0.25,0.5,0.75,1,2,4,8,24,and 48 h after the administration,and the pharmacokinetic parameters of agarotetrol,isoliquiritigenin,piperine,and ferulic acid in the plasma were determined.Results:Most of the peak time of the pharmacokinetics parameters of agarotetrol,isoliquiritigenin,piperine,and ferulic acid in the plasma were 1 to 8 h,0.25 h,0.25 to 8 h,and 0.25 h respectively.C_(max) was 140±53.9,8.31±6.34,33.4±22.2,and 15.7±7.90 ng/mL,respectively.t_(1/2) was 10.1±3.85,8.51±4.23,4.45±1.35,and 67.3±55.1 h,respectively.AUC_(0-t) was 1890±1440,45.6±14.3,288±150,and 443±165 h×ng/mL,respectively.MRT_(0-∞) was 13.2±7.45,9.80±4.27,4.91±1.34,and 103±77.1 h,respectively.The main pharmacokinetics parameters of agarotetrol,isoliquiritigenin,and piperine in rats did not show significant statistical significance(P>0.05),while the main pharmacokinetics parameters of ferulic acid(C_(max) and AUC)_(0-t))showed significant statistical significance(P<0.05).Conclusion:This study established a research method for the pharmacokinetics of four components,namely agarotetrol,isoliquiritigenin,piperine,and ferulic acid,after repeated administration of Ruyi Zhenbao Tablets and analyzed their pharmacokinetics characteristics to guide the clinical administration cycle and interval.

关 键 词：如意珍宝片 药代动力学 高效液相色谱串联质谱法 藏药 沉香四醇 异甘草素 胡椒碱 阿魏酸 

分 类 号：R29[医药卫生—民族医学]