注射用黄芩苷镁盐冻干粉在大鼠体内的药代动力学及组织分布
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摘要
目的:研究尾静脉注射黄芩苷镁盐后药物在大鼠体内的药代动力学和组织分布特征,比较黄芩苷镁盐和黄芩苷的药代动力学差异。方法:大鼠尾静脉注射黄芩苷镁盐和黄芩苷后,在不同时间点眼眶取血,采用HPLC测定各时间点的药物浓度,绘制药-时曲线,利用DAS 3. 0软件计算药代动力学参数,应用SPSS 19. 0软件进行统计学分析。尾静脉注射黄芩苷镁盐后,于不同时间点检测药物在心、肝、脾、肺、肾中的质量分数。结果:当黄芩苷镁盐给药剂量为25～100 mg·kg~(-1)时,药时曲线下面积AUC_(0-t)和AUC_(0-∞)与剂量呈良好的线性关系(r <0. 95),而其他药代动力学参数各剂量组间大部分无明显差异。与黄芩苷等摩尔剂量组比较,黄芩苷镁盐中剂量组的平均驻留时间(MRT_(0-t))显著增高。静脉注射黄芩苷镁盐0. 25 h后各组织中药物浓度最高,至0. 75 h时目标成分质量分数迅速降低,其中肾脏中分布最多,其次是肺,在心、肝和脾中分布量较少。结论:注射给药后,黄芩苷镁盐能迅速在体内分布且快速消除,其主要从肾脏排泄。
Objective: To study on the pharmacokinetics and tissue distribution of baicalin magnesium salt in rats after tail vein injection,and compare pharmacokinetic differences between baicalin magnesium salt and baicalin. Method: After tail vein injection of baicalin magnesium salt and baicalin,orbital blood was collected at different time points. The drug concentration was measured by HPLC, the drug concentration-time curve was plotted,the pharmacokinetic parameters were calculated with DAS 3. 0 software,SPSS 19. 0 software was used for statistical analysis. At the same time, the drug distribution in heart, liver, spleen, lung and kidney was measured at different time points after tail vein injection of baicalin magnesium salt. Result: When the dose of baicalin magnesium salt was 25-100 mg·kg~(-1),area under the curve( AUC_(0-t) and AUC_(0-∞)) showed a good linear relationship with the dose( r > 0. 95), but most of the other pharmacokinetic parameters had no significant difference between different dose groups. The mean residence time( MRT_(0-t)) of medium dose group of baicalin magnesium salt was significantly higher than that of equal molar dose group of baicalin. After intravenous injection of baicalin magnesium salt,the drug concentration was the highest in each tissue at 0. 25 h,and the concentration of target component decreased rapidly at 0. 75 h. The distribution of target component in kidney was the most,followed by lung. Conclusion: After injection,the baicalin magnesium salt can be rapidly distributed and quickly eliminated in vivo,which is mainly excreted from the kidney.
Objective: To study on the pharmacokinetics and tissue distribution of baicalin magnesium salt in rats after tail vein injection,and compare pharmacokinetic differences between baicalin magnesium salt and baicalin. Method: After tail vein injection of baicalin magnesium salt and baicalin,orbital blood was collected at different time points. The drug concentration was measured by HPLC, the drug concentration-time curve was plotted,the pharmacokinetic parameters were calculated with DAS 3. 0 software,SPSS 19. 0 software was used for statistical analysis. At the same time, the drug distribution in heart, liver, spleen, lung and kidney was measured at different time points after tail vein injection of baicalin magnesium salt. Result: When the dose of baicalin magnesium salt was 25-100 mg·kg~(-1),area under the curve( AUC_(0-t) and AUC_(0-∞)) showed a good linear relationship with the dose( r > 0. 95), but most of the other pharmacokinetic parameters had no significant difference between different dose groups. The mean residence time( MRT_(0-t)) of medium dose group of baicalin magnesium salt was significantly higher than that of equal molar dose group of baicalin. After intravenous injection of baicalin magnesium salt,the drug concentration was the highest in each tissue at 0. 25 h,and the concentration of target component decreased rapidly at 0. 75 h. The distribution of target component in kidney was the most,followed by lung. Conclusion: After injection,the baicalin magnesium salt can be rapidly distributed and quickly eliminated in vivo,which is mainly excreted from the kidney.
引文
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[12]刘瑞新,李宇辉,高晓洁,等.清开灵注射液中水难溶性成分在不同条件下的表观溶解度测定[J].中国现代中药,2016,18(8):1042-1047.
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[14]肖兰,张晓杰,王峰,等.正常及脑缺血-再灌注大鼠静脉注射清开灵后黄芩苷在脑、肝、肺中的分布[J].中南药学,2016,4(3):166-169.
[15]王文娟,任欢欢,韩吉春,等.黄芩苷抗脑缺血再灌注损伤的作用机制[J].中国实验方剂学杂志,2016,22(1):113-116.
[2] XING J,CHEN X Y,ZHONG D F. Absorption and enterohepatic circulation of baicalin in rats[J]. Life Sci,2005,78(2):140-146.
[3]许海舰,刘一鑫,王志轩,等.黄芩苷镁盐的稳定性研究[J].中国药房,2017,28(22):3076-3079.
[4]刘翠哲,王志轩,苗策禹,等.一种黄芩苷镁化合物及其制备方法与它的用途:中国,CN105732753A[P].2016-07-06.
[5]金鹏,许海舰,徐宝欣,等.黄芩苷研究现状及其镁盐研究前景[J].中国实验方剂学杂志,2017,23(20):228-234.
[6] Park S W,Lee C H,Kim Y S,et al. Protective effect of baicalin against carbon tetrachloride-induced acute hepatic injury in mice[J]. J Pharmacol Sci,2008,106(1):136-143.
[7] PENG X D,DAI L L,HUANG C Q,et al. Correlation between anti-fibrotic effect of baicalin and serum cytokines in rat hepatic fibrosis[J]. World J Gastroenterol,2009,15(37):4720-4725.
[8]孙设宗,唐微,张红梅,等.镁离子、山药多糖对四氯化碳肝损伤的保护作用[J].中国现代医学杂志,2009,19(12):2780-2786.
[9]张喜平,程琪辉,沈培红,等.黄芩苷类注射剂安全性与急性毒性实验研究[J].医学研究杂志,2007,36(7):15-21.
[10]许海舰,刘一鑫,常金花,等.大鼠体内黄芩苷镁盐分析方法建立[J].亚太传统医药,2017,13(24):10-13.
[11]许海舰,刘一鑫,刘喜刚,等.黄芩苷镁盐和黄芩苷的肠吸收动力学和药代动力学比较[J].中国实验方剂学杂志,2018,24(4):78-83.
[12]刘瑞新,李宇辉,高晓洁,等.清开灵注射液中水难溶性成分在不同条件下的表观溶解度测定[J].中国现代中药,2016,18(8):1042-1047.
[13]卢禹婷,易艳,李春英,等.双黄连注射液的类过敏反应特点及影响因素分析[J].中国实验方剂学杂志,2015,21(9):97-101.
[14]肖兰,张晓杰,王峰,等.正常及脑缺血-再灌注大鼠静脉注射清开灵后黄芩苷在脑、肝、肺中的分布[J].中南药学,2016,4(3):166-169.
[15]王文娟,任欢欢,韩吉春,等.黄芩苷抗脑缺血再灌注损伤的作用机制[J].中国实验方剂学杂志,2016,22(1):113-116.