基于阿魏酸和丹酚酸B在大鼠血浆的药动学研究阿魏酸和丹参多酚酸联合用药

目的:通过对阿魏酸及丹酚酸B在大鼠体内的药动学相互影响,进而探讨阿魏酸和丹参多酚酸联合用药。方法:大鼠随机分为3组:阿魏酸组(0.5 mg·kg^-1)、丹参多酚酸组(以丹酚酸B计给药50 mg·kg^-1)、阿魏酸与丹参多酚酸联合组(阿魏酸0.5 mg·kg^-1、丹参多酚酸以丹酚酸B计给药50 mg·kg^-1),尾静脉注射药物,在不同时间点采集血样,血浆经乙酸乙酯液液萃取后,采用UPLC测定血浆中丹酚酸B和阿魏酸的药物浓度,分别利用WinNonlin 6.2软件和SPSS软件求算动力学参数和统计学分析。结果:全面考察了线性方程、稳定性、重复性、精密度及回收率等在内的方法学,结果表明所建立的分析方法和样品处理方法稳定可靠。经药代动力学及统计软件分析显示单用与联合用药的主要药动学参数如半衰期(t_1/2)、表观分布容积(V_d)、清除率(CL)、药时曲线下面积(AUC)等均有显著性差异。结论:阿魏酸和丹参多酚酸联合用药显著影响药效成分阿魏酸及丹酚酸B在大鼠体内的药动学过程,两药联用抑制阿魏酸的分布、加快清除、缩短作用时间;丹酚酸B情况与阿魏酸趋势相同,但影响要小些;通过比较阿魏酸和丹酚酸B的药动学参数,联合用药有导致其生物利用度降低的趋势。

Combination of ferulic acid and salvianolate based on pharmacokinetics of ferulic acid and salvianolic acid B in rat plasma

OBJECTIVE To investigate combination of ferulic acid and salvianolate based on pharmacokinetics of ferulic acid and salvianolic acid B in rat plasma.METHODS Rats were randomly divided into three groups to receive intravenous infusion of single ferulic acid (0.5 mg·kg^-1),single salvianolate (equivalent to 50 mg·kg^-1 salvianolic acid B),combination of ferulic acid (0.5 mg·kg^-1) and salvianolate (equivalent to 50 mg·kg^-1 salvianolic acid B),respectively.Blood samples were collected at different time points after intravenous infusion of drugs to SD rats.Plasma was purified by liquid-liquid extraction and analyzed using chloramphenicol as internal standard by UPLC.Pharmacokinetic parameters of ferulic acid and salvianolic acid B were obtained with WinNonlin 6.2 software and analyzed thoroughly by statistical software.RESULTS Full validation of UPLC method was performed,including calibration curves,accuracy,precision,repeatability and recoveries.The developed analytical method and purified plasma method were rapid,sensitive and reliable.There were somewhat or even significant differences in major pharmacokinetic parameters of ferulic acid and salvianolic acid B for combination of ferulic acid and salvianolate compared to ferulic acid or salvianolate alone.These major pharmacokinetic parameters were terminal half-life (t_1/2),apparent volume of distribution (V_d),clearance (CL),area under plasma concentration time curve (AUC).CONCLUSION Drug combination of ferulic acid and salvianolate can inhibit distribution of drugs,increase blood drug concentrations and shorten action times of ferulic acid and salvianolic acid B in vivo.Two drug combination can lead to lower bioavailability compared to single drug.