摘要
目的:研究五味子提取物对氯吡格雷在大鼠体内药代动力学的影响。方法:18只SD大鼠随机平均分成3组,分别为:单用组(单用氯吡格雷)、联用1次组(五味子灌胃1次和氯吡格雷联用)和联用6 d组(五味子灌胃6 d和氯吡格雷联用)。单用组禁食12 h;联用1次组大鼠禁食12 h后,灌胃五味子提取物2.4 mg·kg-11次;联用6 d组大鼠禁食12 h后,每日灌胃五味子提取物2.4 mg·kg-1,持续6 d。3组大鼠均予灌胃氯吡格雷30mg·kg-1。给药后尾静脉采血,用HPLC法测定氯吡格雷羧酸代谢物SR26334的血药浓度,DAS(数据采集系统)计算其药代动力学参数,并统计分析。结果:联用1次组SR26334的AUC(0-t)、AUC(0-∞)、C max、Cl z/F、T max、t1/2z与单用组比较,无显著性差别(P>0.05)。联用6 d组SR26334的AUC(0-t)、AUC(0-∞)、C max明显低于单用组(P<0.05),Cl z/F显著高于单用组(P<0.05),两组SR26334的T max、t1/2z比较无统计学意义(P>0.05)。结论:五味子提取物和氯吡格雷联合用于大鼠时,五味子提取物一次给药,不影响氯吡格雷的体内代谢;五味子提取物长期给药,会使氯吡格雷羧酸代谢产物SR26334的AUC和Cmax减少。临床上两药联合使用时,要注意氯吡格雷的用量,并且加强其药学监护。
Objective：This study is to investigate the effects of Schisandra chinensis Baill on Clopidogrel＇s pharmacoki- netic for rats. Methods ： Eighteen Sprague - Dawley rats were randomly divided into 3 groups （ n = 6） ： Group C （ Clopi- dogrel without Schisandra chinensis Bai） ,Group CSl （Clopidogrel with Schisandra chinensis Baill poured for 1 time） and Ggroup CS6（Clopidogrel with Schisandra chinensis Baill poured for 6 days）. In Group C, rats were fasted for 12 h. While in Group CS1, 2.4 mg kg- 1 of the extract of Schisandra chinensis Baill was given orally for 1 time after the rats were fasted for 12 h. And in Group CS6, after the rats were fasted for 12 h. ,2.4 mg kg^-1 of the extract of Schisandra chinensis Baill was given orally for 6 days. Then all the rats were given 30 mg kg · Clopidogrel orally. Blood samples were taken from the tail vein at multipoints after garage for determination of plasma SR26334 concentration by HPLC. The pharmacokinetic parameters of three groups were calculated by Drug And Statistics soft version 2.0. Then Group C and GroupCS1, Group C and Group CS6 were comparable with respect to pharmacokinetic parameters. Results：No differences between Group C and Group CS1 in Cmax,AUC（0-t） ,AUC（0-∞）,Clz/F,Tmax and t1/2zwere found（P 〉0.05）. AUC（0-t） , AUC（0-∞）, C of SR26334 in Group CS6 was significantly lower than that in Group C （P 〈 0.05 ）. Clz/F of SR26334 in Group CS6 was significantly higher than that in Group C （ P 〈 0.05 ）. Also there was no difference between Group CS6 and Group C in Tmax and t1/2z （ P 〉 0.05 ）. Conclusion ： When Schisandra chinensis Baill and Clopidogrel are both used in rats for one time, Schisandra chinensis Baill can not influence the pharmacokinetics of Clopidogrel. But for a long time. / Schisandra chinensis Baill reduce AUC and Cmax of Clopidogrel＇s carboxylic acid metabolite SR26334. When both twt / drugs are used in clinieal application for a long time, the dosage of Clopidogrel should be
出处
《中华中医药学刊》
CAS
2013年第9期2024-2027,共4页
Chinese Archives of Traditional Chinese Medicine
基金
温州市科技计划项目(Y20100262)
