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目的:建立用于同时测定大鼠血浆中单硝酸异山梨酯、阿魏酸的HPLC-UV分析方法,并用于研究单硝酸异山梨酯与阿魏酸在大鼠体内药动学的相互作用。方法:将18只雄性SD大鼠随机分成单硝酸异山梨酯组、阿魏酸钠组以及硝酸异山梨酯和阿魏酸钠联合给药组,于给药后规定时间点采集血样,HPLC-UV法测定二者的血药浓度,采用DAS 2.0药动学软件处理血药浓度数据,用SPSS 19.0统计学软件对所得药动学数据进行统计学差异分析。结果:大鼠静脉注射单硝酸异山梨酯和阿魏酸钠后,两药单用以及联用的药动学过程均为三室模型。联合用药后,单硝酸异山梨酯的Vd和CL与单独用药时相比显著性降低,而阿魏酸的Vd、CL和t1/2与单独用药时相比显著性增加,两药的其他药动学参数MRT,AUC0-t则无显著性变化。结论:本方法可用于大鼠体内单硝酸异山梨酯和阿魏酸的药动学研究。单硝酸异山梨酯和阿魏酸钠联合用药后各自的药动学参数均发生明显变化,两药有药动学的相互作用。
OBJECTIVE: To establish a HPLC-UV method for the simultaneous determination of isosorbide mononitrate and ferulic acid in rat plasma and to study the pharmacokinetics of isosorbide mononitrate and ferulic acid in rats. Methods: Eighteen male Sprague-Dawley rats were randomly divided into isosorbide mononitrate group, sodium ferulate group and isosorbide dinitrate and sodium ferulate in combination group, blood samples were collected at the prescribed time points after administration, and HPLC- The plasma concentrations of both drugs were determined by UV method. The plasma concentration data were processed by DAS 2.0 pharmacokinetic software. Statistical analysis of the pharmacokinetic data was performed using SPSS 19.0 statistical software. RESULTS: After iv injection of isosorbide mononitrate and sodium ferulate in rats, the pharmacokinetics of the two drugs alone and in combination were three-compartment model. Vd and CL of isosorbide mononitrate were significantly lower than those of the other drugs alone after treatment, while Vd, CL and t1 / 2 of ferulic acid were significantly increased compared with those of the other drugs alone Dynamic parameters MRT, AUC0-t no significant change. Conclusion: This method can be used to study the pharmacokinetics of isosorbide mononitrate and ferulic acid in rats. The pharmacokinetic parameters of isosorbide mononitrate and sodium ferulate were significantly changed after their combination with each other. The two drugs had the pharmacokinetic interaction.