基于药效学与药代动力学的枸杞与华法林在大鼠体内的协同作用  

Pharmacodynamics and pharmacokinetics of lycium barbarum and warfarin in rats Synergistic effect

作　　者：周丽婷 丁珊 陈芳伟 方盈盈 陈悦迪 叶岩荣 ZHOU Liting;DING Shan;CHEN Fangwei;FANG Yingying;CHEN Yuedi;YE Yanrong(Department of Pharmacy,Zhongshan Hospital,Fudan University(Xiamen Branch),Fujian,Xiamen 361015,China;Department of Pharmacy,Zhongshan Hospital,Fudan University,Shanghai 200032,China)

机构地区：[1]复旦大学附属中山医院厦门医院药剂科,福建厦门361015 [2]复旦大学附属中山医院药剂科,上海200032

出　　处：《中国医药科学》2024年第23期57-60,共4页China Medicine And Pharmacy

基　　金：中国药学会科技开发中心科普研究重点项目(CMEI2024KPYJ001228)。

摘　　要：目的研究枸杞在大鼠体内对华法林抗凝作用的影响。方法将大鼠随机分6组:空白组、华法林组、枸杞组及华法林与枸杞的低、中、高3个剂量联用组,设定系列采血点时间。测定凝血酶原时间并计算国际标准化比值(INR)。采用高效液相色谱法并测定大鼠体内华法林血药浓度,用DAS 2.0软件计算药代动力学参数。结果华法林组与空白组、枸杞组INR比较,差异无统计学意义(P>0.05);而在给药24、48、72、96 h后,中剂量组、高剂量组INR高于华法林组,差异有统计学意义(P<0.05);在给药24、48、72 h后,中剂量组、高剂量组华法林血药浓度高于华法林组,差异有统计学意义(P<0.05);华法林组与中剂量组、高剂量组比较,药代动力学参数t_(1/2)、曲线下面积、面积-时间曲线下面积和平均滞留时间,差异有统计学意义(P<0.05),T_(max)、CL_(z)/F和V_(z)/F差异无统计学意义(P>0.05)。结论一定剂量的枸杞与华法林联用能产生协同作用,提高大鼠体内的血药浓度和药效指标,增加抗凝作用。Objective To investigate the effects of Lycium barbarum on the anticoagulant effect of warfarin in rats.Methods Rats were randomly divided into 6 groups,including the blank group,the warfarin group,the Lycium barbarum group and 3 dose combination groups of warfarin and Lycium barbarum in low,moderate and high doses.The time of serial blood collection points was set.The prothrombin time was determined and the international normalised ratio(INR)was calculated.High performance liquid chromatography was used and the blood concentration of warfarin in rats was determined.The pharmacokinetic parameters were calculated using DAS 2.0 software.Results There was no significant difference in INR between warfarin group,blank group and Lycium barbarum group(P>0.05).At 24,48,72 and 96 h after administration,INR in medium dose and high dose groups was higher than that in warfarin group,and the difference was statistically significant(P<0.05).At 24,48 and 72 h after administration,the blood concentration of warfarin in medium dose group and high dose group was higher than that in warfarin group,and the difference was statistically significant(P<0.05).There were statistically significant differences in pharmacokinetic parameters t1/2,area under the curve,area under the area-time curve and average residence time between warfarin group and medium dose group and high dose group(P<0.05),while there were no statistically significant differences in T_(max),CL_(z)/F and V_(z)/F between warfarin group and medium dose group(P>0.05).Conclusion The combination of a certain dose of Lycium barbarum with warfarin can produce synergistic effects,improve the blood concentration and pharmacodynamic indexes in rats and increase the anticoagulant effect.

关 键 词：华法林 枸杞 抗凝作用 药物相互作用 

分 类 号：R285.5[医药卫生—中药学]