高效液相色谱法测定人参炔醇在大鼠体内血药浓度及药动学研究

Concentration of panaxynol in rat plasma determined by high performance liquid chromatography and its pharmacokinetic study

目的:绘制大鼠静脉注射人参炔醇(panaxynol)后血药浓度-时间曲线,揭示人参炔醇在大鼠体内动态变化过程,阐明其吸收、分布、代谢的药动学特征,提供重要的药动学参数。方法:大鼠静脉注射6,8,10 mg·kg^(-1)3组剂量的人参炔醇,给药后分时间段于眼静脉丛取血,高效液相色谱(HPLC)法测人参炔醇含量,绘制血药浓度-时间曲线,利用DAS 1.0软件对数据进行拟合,求算药动学参数及房室模型分析。结果:人参炔醇血-药经时过程符合二室模型;3个剂量组之间的药动学参数无显著性差异,浓度-时间曲线下面积(AUC_(0-t))分别为:(3.628±0.750),(5.492±0.959),(15.468±3.088)mg·h·L^(-1);总清除率(CL)分别为:(1.649±0.365),(1.459±0.267),(0.637±0.147)L·kg·h-1;表观分布容积(V)分别为:(13.104±1.217),(5.738±2.480),(3.355±0.810)L·kg-1;分布半衰期t_(1/2)(α)分别为:(0.198±0.028),(0.193±0.015),(0.296±0.029)h;消除半衰期t_(1/2(β))分别为:(3.972±1.224),(3.168±1.235),(3.713±0.410)h。结论:panaxynol在大鼠体内呈线性动力学过程,分布消除极其迅速,给药剂量与药时曲线下面积呈正相关;二室模型拟合数据值与测定值之间差异较小,能较好地反应给药后药物浓度在体内的变化规律。

OBJECTIVE To draw concentration-time curve after intravneous administration of panaxynol in rats, reveal dynamic changes of panaxynol in rats to clarify its absorption, distribution, metabolism, and provide important pharmacokinetic parameters.METHODS Blood samples were collected from segment venous plexus of the eyes after administering panaxynol at 6, 8, 10 mg·kg^-1panaxynol, then panaxynol content was measured by HPLC to draw concentration-time curve. The data were fitted by DAS 1.0, pharmacokinetic parameters were calculated and the compartmental model was analysed.RESULTS The pharmacokinetics of panaxynol were studied. Pharmacokinetics of panaxynol in rat plasma fit two-compartmental model. After intravenous administration, pharmacokinetic parameters were not significantly different between the three doses. Areas under curve （AUC 0-t）, （3.628±0.750）, （5.492±0.959）, （15.468±3.088） mg·h·L^-1clearance rate （CL）, （1.649±0.365）, （1.459±0.267）, （0.637±0.147） L·kg·h^-1apparent volume of distribution （V）, （13.104±1.217）, （5.738±2.480）, （3.355±0.810） L·kg^-1; distribution half-life t1/2（α）, （0.198±0.028）, （0.193±0.015）, （0.296±0.029） h; elimination half-life t1/2（β）, （3.972±1.224）, （3.168±1.235）, （3.713±0.410） h.CONCLUSION The metabolism of panaxynol in rats is accordant with the linear relationship, and dose and the area under curve are positively correlated. The data of the two-compartmental model fit with the measurements and can reflect drug concentrations in rats after intravenous administration.