参芎葡萄糖注射液在正常和急性心肌缺血大鼠体内的药动学差异
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篇名: 参芎葡萄糖注射液在正常和急性心肌缺血大鼠体内的药动学差异
TITLE: Pharmacokinetic difference of Shenxiong glucose injection in normal and acute myocardial ischemia rats
摘要: 目的 比较参芎葡萄糖注射液(SGI)中盐酸川芎嗪、丹参素、迷迭香酸在正常和急性心肌缺血(AMI)模型大鼠体内的药动学差异。方法将雄性SD大鼠随机分为正常组和模型组,每组9只。模型组大鼠采用盐酸异丙肾上腺素造模法复制AMI模型。每组各取3只大鼠进行模型验证后,剩余6只大鼠尾静脉注射SGI(12mL/kg)或等体积生理盐水,并分别于给药后0.083、0.167、0.333、0.5、0.75、1、1.5、2、3、5h经眼眶静脉丛采血0.3mL。以木犀草苷为内标,采用超高效液相色谱-串联质谱法检测血浆中盐酸川芎嗪、丹参素、迷迭香酸的质量浓度,采用WinNonlin8.1软件拟合药动学参数,采用SPSS18.0软件进行统计学分析。结果盐酸川芎嗪、丹参素、迷迭香酸检测质量浓度的线性范围分别为0.06~29.96、0.01~5.15、0.006~3.09μg/mL(r均大于0.99),方法学考察结果均符合2020年版《中国药典》的相应要求。与正常大鼠比较,AMI模型大鼠体内盐酸川芎嗪的CLz显著升高(P<0.05);丹参素的t1/2和Vz均显著延长或升高(P<0.05),但cmax和AUC0-5h均显著降低(P<0.05);迷迭香酸的AUC0-5h显著降低(P<0.05)。结论SGI中的丹参素、迷迭香酸在AMI模型大鼠体内的暴露量均低于正常大鼠,盐酸川芎嗪在AMI模型大鼠体内的消除强于正常大鼠。
ABSTRACT: OBJECTIVE To compare the phar macokinetics o f ligustrazine hydrochlori de,salvianic acid and rosemarinic acid from Shenxiong glucose injection (SGI)in normal and acute myocardial ischemia (AMI)rats. METHODS Male SD rats were randomly divided into normal group and model group ,with 9 rats in each group. AMI model was established by isoproterenol hydrochloride modeling method. Three rats in each group were selected for model verification. The remaining 6 rats in each group were given SGI (1.2 mL/kg)or equal volum of normal saline via tail vein ;0.3 mL blood was collected through orbital venous bush 0.083,0.167,0.333,0.5,0.75,1,1.5,2,3,5 h after administration. Using luteoloside as internal standard ,the plasma concentrations of ligustrazine hydrochloride ,salvianic acid and rosemarinic acid were determined by ultra performance liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were fitted by WinNonlin 8.1 software,and statistical analysis was performed by SPSS 18.0 software. RESULTS The linear ranges of ligustrazine hydrochloride ,salvianic acid and rosmarinic acid were 0.06-29.96,0.01-5.15 and 0.006-3.09 μ g/mL(all r>0.99),respectively. The results of methodological investigation were all in line with the requirements of Chinese Pharmacopoeia (2020 edition). Compared with normal rats ,CLz of ligustrazine hydrochloride in AMI model rats was significantly increased (P<0.05);t1/2 and Vz of salvianic acid were significantly prolonged or increased (P<0.05);but the cmax and AUC 0-5 h were significantly decreased (P<0.05);AUC0-5 h of rosmarinic acid was significantly decreased (P<0.05). CONCLUSIONS The exposure levels of salvianic acid and rosmarinic acid in SGI are lower in AMI model rats than in normal rats ,and the elimination of ligustrazine hydrochloride in AMI model rats is stronger than that in normal rats.
期刊: 2022年第33卷第04期
作者: 张静雅,刘利琴,李容,陆苑,潘洁,刘亭,孙佳
AUTHORS: ZHANG Jingya ,LIU Liqin,LI Rong,LU Yuan,PAN Jie,LIU Ting,SUN Jia
关键字: 参芎葡萄糖注射液;急性心肌缺血;超高效液相色谱-串联质谱法;药动学;大鼠
KEYWORDS: Shenxiong glucose injection ;acute myocardial
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