川芎嗪对大鼠体外肝灌流液中非索非那定处置的影响  

The Effect of Tetramethylpyrazine on Disposition of Fexfenadine in Isolated Perfusated Rat Liver

作　　者：张如洪[1] 张林枝[2] 揭金阶[1] 王芳[1] 

机构地区：[1]武汉大学人民医院药学部,430060 [2]武汉大学药学院,430070

出　　处：《医药导报》2010年第1期21-24,共4页Herald of Medicine

摘　　要：目的研究川芎嗪(TMP)对非索非那定在大鼠体外肝灌流(IPL)处置中的影响。方法10只SD雄性大鼠随机分为给药组和对照组各5只。给药组灌服30mg·kg-1·d-1的TMP,对照组灌服0.9%氯化钠溶液,均连续14d,于第15天实施循环肝灌流手术,收集灌流液和胆汁。反相高效液相色谱(RP-HPLC)法测定灌流液和胆汁中非索非那定的浓度,3p97计算其主要药动学参数,并用SPSS11.5进行统计学分析。结果给药组和对照组肝灌流液中AUC(0-60)分别为(95016.35±1457.15),(29441.44±675.16)ng·mL-1·min-1,总清除率(CL)分别为(5.93±0.19),(19.52±0.51)mL·min-1,排入胆汁的非索非那定总量Ae(0-60)分别为(77559.93±9758.37),(135145.16±16211.82)ng,以及胆汁清除率(CLb)分别为(0.82±0.24),(4.59±1.17)mL·min-1,两组差异均有极显著性(均P<0.01),但两组间的分布容积差异无显著性(P>0.05)。结论连续14d服用高剂量的TMP能显著改变P-糖蛋白(P-gp)底物非索非那定在大鼠肝脏的药动学参数,这可能与TMP下调P-gp的表达有关。Objective To investigate the effect of tetramethylpyrazine（TMP） on disposition of fexofenadine in isolated perfusate of rat liver. Methods SD male rats were divided into two groups randomly： treatment group and control group （5 rats respectively）. Rats were i.g. 30 mg ·kg^-1·d^-1 tetramethylpyrazine suspension and the same volume of distilled water for consecutive 14 days. At the 15th day, rat livers were isolated and perfused in a recirculating system, and the both perfusate and bile was collected. The concentrations of fexofenadine in perfusate and bile were determined by RP-HPLC. The main pharmacokinetic（PK） parameters were calculated by 3p97 and statistic analysis was conducted by spss 11.5. Results The AUC（0-60）were 95 016.35±1457. 15 and 29 441.44±675. 16 （ng·mL^-1·min^-1）, total clearance were 5.93 ±0.19 and 19.52 ±0.51（mL·min^-1 ） , the total amount excreted into bile Ae（0-60） were 77 559.93 ±9 758.37 and 135 145.16 ± 16 211.82 （ rig）, the biliary clearance CLb were 0.82 ± 0.24 and 4.59 ± 1.17 （ mL·min^-1 ） for treatment group and control group, respectively. There was a significant difference between them （P 〈 0.01 ）, but not the volume of distribution V（mL）. Conclusion Administration of tetramethylpyrazine at a high dose for 14 consecutive days can significantly change the PK parameters of P-gp substrate fexofenadine in rat livers, which is likely related to down regulation of P-gp.

关 键 词：川芎嗪 非索非那定 色谱法 高效液相 P-糖蛋白 

分 类 号：R286[医药卫生—中药学] R965[医药卫生—中医学]