水飞蓟素对大鼠体内他莫昔芬药动学的影响

Effects of Silymarin on Pharmacokinetics of Tamoxifen in Rats

目的:研究水飞蓟素对大鼠体内他莫昔芬药动学的影响。方法:色谱柱为KromasilC18(250mm×4.6mm,5μm),流动相为乙腈-20mmol/LK2HPO4水溶液(70:30,V:V,磷酸调pH值至3.0),流速为1.0ml/min,柱温为45℃,检测波长λex=260nm,λem=375nm。对照组大鼠灌胃他莫昔芬丙二醇溶液(15mg/kg),实验组大鼠在灌胃水飞蓟素水溶液(70mg/kg)30min后灌胃他莫昔芬丙二醇溶液(15mg/kg)。测定不同时间2组大鼠血药浓度,以DAS2.1.1版药动学程序软件计算药动学参数。结果:与对照组比较,实验组的cmax显著增加(P<0.05),AUC0-36h和AUC0-∞分别增加了52.7%～80.1%和56.4%～82.1%(P=0.005),CL/F降低了29.5%～41.3%(P=0.005),而t1/2和tmax没有显著性差异。结论:水飞蓟素对大鼠体内他莫昔芬的药动学有显著影响,临床上二者合用时应注意潜在的药物相互作用。

OBJECTIVE：To study the effects of silymarin on pharmacokinetics of tamoxifen in rats.METHODS：The analysis was performed on a Kromasil C 18（250 mm×4.6 mm,5 μm）column,with the acetonitrile-20 mmol/L K 2 HPO 4（70：30,V：V,phosphoric acid to adjust the pH value to 3）as the mobile phase.The flow rate was 1.0 mL/min,Column temperature was 45 ℃,and the detective wave length were λ ex =260 nm,λ em =375 nm.Control group was given tamoxifen propylene glycol solution intragastrically（15 mg/kg）;trial group was given silymarin solution 70 mg/kg,and received tamoxifen propylene glycol solution 15 mg/kg intragastrically 30 min later.Blood concentration of tamoxifen was determined by HPLC.The data were calculated by DAS2.0 software.RESULTS：Compared with control group,c max of tamoxifen in trial group was increased significantly（P〈0.05）,AUC 0-36 h and AUC 0-∞ of tamoxifen was increased by 52.7%-80.1% and 56.4%-82.1%（P=0.005）,respectively;CL/F of tamoxifen was decreased by 29.5%-41.3%（P=0.005）,and no change of t max and t 1/2 was observed.CONCLUSIONS：There is significant effect of silymarin on tamoxifen in rats.Great importance should be attached to drug interaction during combined use of them in the clinic.