摘要
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 an HPLC-UV method for the determination of isosorbide mononitrate and ferulic acid simultaneously in rat plasma, and to explore the pharmacokinetic interaction between isosorbide mononitrate and ferulic acid. METHODS 18 male Sprague-Dawley rats were divided into isosorbide mononitrate group,metronidazole group, aminophylline and metronidazole group randomly. Blood samples were collected at intervals after each intervenous administration. Then the concentration of isosorbide mononitrate and ferulic acid was determined by HPLC-UV, and the pharmacokinetic parameters were calculated by DAS 2. 0 software and were compared by SPSS 19. 0 software. RESULTS The plasma concentration-time curves of isosorbide mononitrate and ferulic acid （both signal and combined groups） were both fitted three-compartment model after intervenous administration. Compared with signal groups, the pharmacokinetic parameters Vd and CL of the isosorbide mononitrate significantly decreased, meanwhile, the pharmacokinetic parameters Vd, CL and tl/2 of the ferulic acid were elevated. The MRT,AUCtof the two drugs had no obviously changed. CONCLUSION The method is suitable for the pharmacokinetic study of isosorbide mononitrate and ferulic acid in rat plasma. Obtained pharmacokinetic parameters showed significant differ- ences after combined-use of isosorbide mononitrate and ferulic acid, indicating there is a dru~ interaction on each other.
出处
《中国医院药学杂志》
CAS
CSCD
北大核心
2013年第5期377-381,共5页
Chinese Journal of Hospital Pharmacy
关键词
单硝酸异山梨酯注射液
注射用阿魏酸钠
药动学
相互作用
isosorbide mononitrate injection
sodium ferulate for injection
pharmacokinetics
interaction
