六味地黄丸对大鼠肝CYP1A2及肠道P-gp活性的影响

Effect of Liuwei Dihuang Pill on the activity of liver CYP1A2 and P-gp in rat intestines

目的:考察六味地黄丸对大鼠肝CYP1A2及肠道P-gp活性的影响。方法:两组(各5只)大鼠分别灌胃给予六味地黄丸生理盐水7 d后,静脉给予咖啡因,用HPLC法测定咖啡因的血药浓度,获得药-时曲线,计算药动学参数,以咖啡因t1/2的变化来评价六味地黄丸对大鼠肝CYP1A2活性的影响;采用在体肠循环法,通过分析P-gp底物地高辛肠吸收参数的变化来考察六味地黄丸对P-gp活性的影响。结果:生理盐水组、六味地黄丸组大鼠体内探针药物咖啡因的t1/2分别为(2.61±0.98)h、(5.14±0.21)h;地高辛在给药组和对照组肠吸收百分率分别为(6.54±0.71)%、(5.42±0.23)%,吸收速率常数分别为(0.030±0.005 7)h-1、(0.024±0.003 9)h-1。结论:六味地黄丸对大鼠肝CYP1A2活性具有一定抑制作用,对肠道P-gp活性具有较弱的诱导作用。

AIM：To investigate the effect of Liuwei Dihuang Pill（LWDHP） on the activity of CYP1A2 and P-gp in rat intestines.METHODS：After orally administering LWDHP and normal saline for 7 days,resectively for LWDHP group（5） and control group（5） caffeine was given intravenously at a dose of 10 mg/kg.A developed HPLC method was used to determine the concentrations of caffeine in rat plasma and calculate pharmacokinetic pa-rameters.Thange in caffeine t1/2 was used to evaluate LWDHP on the activity of rat CYP1A2.The absorption kinet-ics of digoxin at rats intestine was studied by in situ recirculation and the absorption parameters were used to evalu-ate the effect of LWDHP on P-gp.RESULTS：The t1/2 values of caffeine in groups of LWDHP and control group were（2.61 ±0.98） h、（5.14 ±0.21） h,respectively.The absorption rate constants（Ka） in LWDHP and control group were（0.030 ±0.005 7） h-1、（0.024 ±0.003 9） h-1,respectively.The absorption percentage in one hour of intestines were（6.54 ± 0.71）% and（5.42 ± 0.23）% for LWDHP and control group,respectively.CON-CLUSION：Liuwei Dihuang Pill has an inhibitive effect on rats’CYP1A2 and a weaker inductive influence on P-gp in rat intestines.