蓬子菜中香叶木苷对华法林在大鼠体内药动学和药效学影响的研究  

Effects of diosmin from Galium verum L.on pharmacokinetics and pharmacodynamics of warfarin in rats

作　　者：崔明宇[1] 隋玥 胡启萌 朱凤梅 尹义凤 于超 阎雪莹[1] 苏慧[1] CUI Mingyu;SUI Yue;HU Qimeng;ZHU Fengmei;YIN Yifeng;YU Chao;YAN Xueying;SU Hui(Heilongjiang University of Chinese Medicine,Harbin 150040,Heilongjiang,China)

机构地区：[1]黑龙江中医药大学,黑龙江哈尔滨150040

出　　处：《现代中西医结合杂志》2023年第1期19-24,共6页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：黑龙江省自然科学基金项目(H2015044,LH2020H096);黑龙江中医药大学研究生创新项目(2022yjscx053);黑龙江省中医药科研项目(ZHY-2022-117)。

摘　　要：目的研究蓬子菜中香叶木苷对单剂量和稳态华法林在大鼠体内药动学和药效学的影响。方法将24只雄性SD大鼠随机分为4组,每组6只。单剂量华法林组给予0.5%CMC-Na液灌胃,单剂量华法林+香叶木苷组给予香叶木苷药液80.00 mg/kg灌胃,均连续7 d;第8天,2组再分别给予华法林药液0.25 mg/kg灌胃1次。华法林稳态组、华法林稳态+香叶木苷组每天给予华法林药液0.25 mg/kg灌胃,连续8 d;第5天起,华法林稳态组同时给予0.5%CMC-Na液灌胃,华法林稳态+香叶木苷组同时给予香叶木苷药液80.00 mg/kg灌胃。给药后于不同时间点采集血浆样品,测定血药浓度,DAS 2.0计算主要药动学参数(C_(max),t_(1/2),AUC_((0-t)),AUC_((0-∞)));测定凝血酶原时间(PT),计算国际标准化比值(INR)。结果单剂量华法林+香叶木苷组的C _(max),t_(1/2),AUC_((0-t)),AUC_((0-∞))和血药浓度均较单剂量华法林组有所升高,但2组比较差异均无统计学意义(P均>0.05);单剂量华法林+香叶木苷组PT明显长于单剂量华法林组(P<0.05),INR明显高于单剂量华法林组(P<0.05)。华法林稳态+香叶木苷组联合用药后第1,2,3天华法林的血药浓度均较华法林稳态组有所升高,但2组比较差异均无统计学意义(P均>0.05);华法林稳态+香叶木苷组PT明显长于华法林稳态组(P<0.05),INR明显高于华法林稳态组(P<0.05)。结论香叶木苷与华法林联合应用可延长PT,升高INR,二者联合应用时应监测PT和INR,以免发生出血。Objective It is to study the effect of diosmin from Galium verum L.on pharmacokinetics and pharmacodynamics of single-dose and steady-state warfarin in rats.Methods Twenty-four male SD rats were divided into 4 groups,with 6 rats in each group.The single-dose warfarin group was given 0.5%CMC-Na solution by gavage,and the single-dose warfarin+diosmin group was given diosmin solution 80.00 mg/kg by gavage,both the two groups were treated for 7 days;on the 8th day,they were given warfarin solution 0.25 mg/kg by gavage for one time.The warfarin steady state group and warfarin steady state+diosmin group were given warfarin 0.25 mg/kg by gavage daily,totally for 8 days;from the 5th day,the warfarin steady state group was also given 0.5%CMC-Na solution by gavage,and the warfarin steady state+diosmin group were given also given diosmin solution 80.00 mg/kg by gavage.The plasma samples were collected at different time points after administration to measure blood concentrations,and main pharmacokinetics parameters(C max,AUC_((0-t))and AUC_((0-∞)))were calculated by DAS 2.0;the prothrombin time(PT)was determined and international normalized ratio(INR)was calculated.Results The C max,AUC_((0-t))and AUC_((0-∞))and blood concentration in the single-dose warfarin+diosmin group were higher than those in the single-dose warfarin group,but the differences between the two groups were not statistically significant(P>0.05).The PT in the single-dose warfarin+diosmin group was significantly loner than that in the single-dose warfarin group(P<0.05),and the INR was significantly higher than that in the single-dose warfarin group(P<0.05).In the warfarin steady-state+diosmin group,the blood concentration of warfarin was higher than that in the warfarin steady-state group on the 1st,2nd and 3rd day after the combination,but the differences between the two groups were not statistically significant(P<0.05).In the warfarin steady-state+diosmin group,the PT was significantly longer than that in the warfarin steady-state group(P<0.05),and the

关 键 词：蓬子菜 香叶木苷 华法林 药动学 药效学 药物相互作用 

分 类 号：R-332[医药卫生]