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

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.