丁苯酞对大鼠体内硝苯地平药动学的影响研究

目的:研究丁苯酞对大鼠体内硝苯地平药动学的影响。方法:取大鼠随机分为对照组(硝苯地平10mg·kg-1)和实验组(硝苯地平10mg·kg-1+丁苯酞80mg·kg-1),每组6只,灌胃给予相应药物,于给药前和给药后0·08、0·25、0·33、0·5、1、1·5、2、2·5、3、4、5h眼底静脉丛取血0·5mL,采用高效液相色谱法测定血药浓度,以DAS2·1·1药动学程序拟合药动学参数。色谱柱为Diamon-silTMC18,流动相为乙腈-水(56:44),流速为1·0mL·min-1,检测波长为238nm。结果:硝苯地平检测浓度的线性范围为0·079～5·080μg·mL-1(r=0·9983),提取回收率为75·67%～81·38%,日内、日间RSD均<7%。对照组和实验组硝苯地平的药动学参数分别为AUC0～∞:(8·23±2·23)、(4·14±1·63)mg·h·L-1,cmax:(2·76±0·79)、(1·85±0·55)mg·L-1,t1/2z:(2·9±1·27)、(2·14±0·84)h,CL/F:(2·61±0·79)、(4·96±1·47)L·h-1·kg-1,其中AUC0～∞、cmax、CL/F差异均有统计学意义(P<0·05)。结论:丁苯酞可使大鼠体内硝苯地平吸收减少、消除加快。

Effects of Butylphthalide on the Pharmacokinetics of Nifedipine in Rats

OBJECTIVE:To investigate the effects of butylphthalide on the pharmacokinetics of nifedipine in rats.METHODS:SD rats were randomly divided in control group(nifedipine 10 mg·kg-1) and trial group(nifedipine 10 mg·kg-1+butylphthalide 80 mg·kg-1) with 6 rats in each group.The rats were received relevant drugs intragastrically,and blood samples were collected from fundus venous plexus 0.5 mL each time before treatment and 0.08,0.25,0.33,0.5,1,1.5,2,2.5,3,4,5 h after treatment.The blood concentration of drugs was determined by HPLC,and the pharmacokinetic parameters were calculated by DAS2.1.1 program.The determination was performed on DiamonsilTM C18 column with mobile phase consisted of acetonitrile-water(56:44) at a flow rate of 1.0 mL·min-1.The detection wavelength was set at 238 nm.RESULTS:The linear range of nifedipine was 0.079～5.080 μg·mL-1(r=0.998 3)with an average extraction recovery of 75.67%～81.38%.The RSD of intra-day and inter-day were all lower than 7%.The pharmacokinetic parameters of nifedipine in control group vs.trail groups were as follows:AUC0～∞:(8.23±2.23) mg·h·L-1 vs.(4.14±1.63) mg·h·L-1;cmax:(2.76±0.79) mg·L-1 vs.(1.85±0.55) mg·L-1;t1/2z:(2.9±1.27) h vs.(2.14±0.84) h;CL/F:(2.61±0.79) L·h-1·kg-1 vs.(4.96±1.47) L·h-1·kg-1.There was statistical significance in the difference in AUC0～∞,cmax and CL/F between 2 groups(P<0.05).CONCLUSIONS:Butylphthalide can inhibit the absorption of nifedipine in rats.