贯叶连翘对大鼠离体肝灌流中非索非那定肝处置的影响  

HPL's effect on the disposition of fexofenadine in the isolated perfused rat liver

作　　者：张如洪[1] 陈亮[2] 揭金阶[1] 张林枝[2] 

机构地区：[1]武汉大学人民医院,湖北武汉430060 [2]武汉大学药学院,湖北武汉430071

出　　处：《中国医院药学杂志》2009年第20期1746-1749,共4页Chinese Journal of Hospital Pharmacy

摘　　要：目的:以非索非那定(Fexofenadine,Fexd)为P-糖蛋白的探针分子,采用大鼠离体肝脏灌流技术(IPRL),评价长期给予贯叶连翘片(每片含900μg金丝桃苷)对大鼠肝脏P-糖蛋白及非索非那定的处置的影响。方法:16只SD♂大鼠被随机分成3组,大鼠体质量(315±65)g,平均周数11±2,差异均无显著性:对照组(灌生理盐水)、低剂量(150mg.kg-1.d-1贯叶连翘混悬液)、高剂量组(500mg.kg-1.d-1贯叶连翘混悬液),连续灌胃14d后禁食18h,施行离体循环肝灌流手术,肝灌流液中加入Fexd,定时收集灌流液和胆汁样品,样品采用HPLC方法检测。结果:3组的灌流液中Fexd药动学参数差异无显著性,胆汁排泄率和胆汁清除率差异有显著性。结论:贯叶连翘是P-糖蛋白(P-GP)的诱导剂,增加由其介导的Fexd的胆汁排泄率和胆汁清除率。OBJECTIVE In this study the overall purpose is to investigate H. perforatum L（HPL） on the modulate the p gly coprotein and on the disposition of fexofinadine in the isolated perfused rat liver. METHODS 16 Sprague-Dawley （SD） male rats randomly into 3 groups： control, low dose 150mg·kg^- 1 ·d ^-1 （of HPL） and high dose 500mg·kg^- 1 ·d ^-1 （of HPL ） , the low dose and high dose group were pre-treated with HPL for 14 conseceutive days via gastric gavage with dose of 1 mL/100 g, then the rats were performed the isolated liver surgery, the livers were then isolated from the systemic circulation and perfused with medium containing Fexofenadine. The perfusate and bile samples were collected to determine the clearance of Fexofenadine and excretion rate in the bile by hepatic P gp. RESULTS There are significant differences in the biliary excretion rate and clearance though no significant differences in the perfusate pharmacokinetic parameters in these 3 groups. CONCLUSION These results indicate that HPL can increase hepatic lyglycoprotein （P-GP） therefore increase biliary excretion rate and clearance.

关 键 词：非索非那定 贯叶连翘 IPRL P-糖蛋白 

分 类 号：R285.6[医药卫生—中药学]