冠脉康缓释胶囊中葛根素在比格犬体内药动特征
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摘要
目的:观察冠脉康缓释胶囊中葛根素在Beagle犬体内的药动学特征,为pH依赖性释放的冠脉康缓释制剂研发提供参考。方法:Beagle犬随机分成两组,单剂量双周期交叉口服冠脉康缓释胶囊与普通胶囊,采用HPLC法测定血浆中葛根素含量,比较各制剂的药动学参数。结果:冠脉康缓释胶囊与普通胶囊中葛根素的主要药代动力学参数:Cmax分别为(81.79±12.60)、(217.41±26.16)μg·L-1;Tmax分别为(2.33±0.52)、(1.33±0.26)h;MRT分别为:(8.71±0.55)、(2.86±0.31)h;AUC0～t分别为(489.97±45.17)、(430.12±9.60)μg·h·L-1。冠脉康缓释胶囊较普通胶囊的相对生物利用度为113%。结论:与普通胶囊相比,冠脉康缓释胶囊在Beagle犬体内吸收较慢,平均滞留时间约为普通胶囊的3倍,生物利用度显著提高,提示冠脉康缓释胶囊可以实现药物在胃肠道中pH依赖性释放。
Objective:To study the pharmacokinetics of puerarin in Guanmaikang Sustained-release Capsule and common capsule in Beagle dogs for providing an reference for pH-dependent release of sustained-release formulations of Guanmaikang. Methods:Beagle dogs were randomly assigned to receive sustained-release capsule and common capsule,then a crossover trial was conducted one week later.Puerarin concentrations in plasma were determined by HPLC to compare pharmacokinetic parameters of each formulation. Results:The main pharmacokinetic parameters of puerarin in test capsule and reference capsule were:Cmax of(81.79±12.60),(217.41±26.16)μg·L-1;Tmax of(2.33±0.52),(1.33±0.26)h;MRT of(8.71±0.55),(2.86±0.31)h;AUC0-t of(489.97±45.17),(430.12±9.60)μg·h·L-1,respectively. Relative bioavailability of sustained-release capsule to common capsule was 123%. Conclusion:Compared with common capsule,Guanmaikang Sustained-release Capsule show slower absorption in Beagle dogs,the average residence time is three times more than the former,relative bioavailability has also been significantly improved,this formulation can achieve pH-dependent release in the gastro intestinal tract.
Objective:To study the pharmacokinetics of puerarin in Guanmaikang Sustained-release Capsule and common capsule in Beagle dogs for providing an reference for pH-dependent release of sustained-release formulations of Guanmaikang. Methods:Beagle dogs were randomly assigned to receive sustained-release capsule and common capsule,then a crossover trial was conducted one week later.Puerarin concentrations in plasma were determined by HPLC to compare pharmacokinetic parameters of each formulation. Results:The main pharmacokinetic parameters of puerarin in test capsule and reference capsule were:Cmax of(81.79±12.60),(217.41±26.16)μg·L-1;Tmax of(2.33±0.52),(1.33±0.26)h;MRT of(8.71±0.55),(2.86±0.31)h;AUC0-t of(489.97±45.17),(430.12±9.60)μg·h·L-1,respectively. Relative bioavailability of sustained-release capsule to common capsule was 123%. Conclusion:Compared with common capsule,Guanmaikang Sustained-release Capsule show slower absorption in Beagle dogs,the average residence time is three times more than the former,relative bioavailability has also been significantly improved,this formulation can achieve pH-dependent release in the gastro intestinal tract.
引文
[1]陈立兵,葛卫红,张继稳.我国中药缓控释制剂的研究状态分析[J].世界科学技术—中医药现代化,2007,9(5):83-90.
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[5]高小明,邹桂欣,张颖.冠脉康颗粒对急性脑缺血小鼠脑组织炎症因子的影响[J].用药物与临床,2018,21(7):753-755.
[6]李显华,邹桂新,杜佳林,等.冠脉康胶囊对大鼠血栓模型及小鼠急性脑缺血模型的影响[J].实用中医内科杂志,2012,26(12):20-21.
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[9]邓向涛,郝海军,贾幼智,等.葛根素磷脂复合物及其固体分散体的药代动力学及生物利用度研究[J].中药材,2015,38(9):1974-1976.
[10]王昌利,董林娟,张文娟,等,正常及心肌缺血大鼠静脉注射葛根提取物后体内药物动力学研究[J].现代中医药,2016,36(4):72-75.
[11]董林娟,张文娟,刘诗雨,等.龙脉宁方中葛根素在心肌缺血大鼠体内药动学-药效学相关性研究[J].中国中药杂志,2016,41(8):1535-1540.
[12]陈小新,原素,李耿,等.葛根素自微乳在Beagle犬体内的药代动力学及生物利用度研究[J].中药材,2011,34(5):750-753.
[13]杜力军,邢东明,炎彬,等.对葛根素与葛根黄酮体内动力学关系的探讨[J].世界科学技术-中医药现代化,2004,6(6):32.
[14]郭宇洁,孟硕,徐辉,等.葛根素和葛根黄酮的药代动力学研究概述[J].中国实验方剂学杂志,2009,15(6):82-85.
[15]崔升淼,赵春顺,毛晶晶,等.乳糖酸红霉素对葛根素药物动力学的影响[J].沈阳药科大学学报,2004,21(6):412-415
[16]赵延礼,潘振宇,于本涛.HPLC法测定大鼠血浆中葛根素含量[J].青海医药杂志,2009,39(4):59-60.
[2]王永霞,何立人.葛根素的心血管系统药理作用及机理研究[J].上海中医药杂志,2004,38(4):62-64.
[3]李显华杜佳林邹桂新,等.冠脉康胶囊对心肌缺血缺氧动物模型的影响[J].实验动物科学,2012,29(1):66-68.
[4]邹桂欣,吴雅崑,尤献民,等.冠脉康抗缺血药效物质基础研究[J].中华中医药学刊,2012,30(7):1537-1538.
[5]高小明,邹桂欣,张颖.冠脉康颗粒对急性脑缺血小鼠脑组织炎症因子的影响[J].用药物与临床,2018,21(7):753-755.
[6]李显华,邹桂新,杜佳林,等.冠脉康胶囊对大鼠血栓模型及小鼠急性脑缺血模型的影响[J].实用中医内科杂志,2012,26(12):20-21.
[7]姚丹,丁选胜.葛根素药理作用机制探讨及临床应用[J].中药临床药理学与治疗学,2008,13(4):468-472.
[8]伟唯,江培.葛根素药理作用研究进展[J].黑龙江医药,2014,27(1):48-52.
[9]邓向涛,郝海军,贾幼智,等.葛根素磷脂复合物及其固体分散体的药代动力学及生物利用度研究[J].中药材,2015,38(9):1974-1976.
[10]王昌利,董林娟,张文娟,等,正常及心肌缺血大鼠静脉注射葛根提取物后体内药物动力学研究[J].现代中医药,2016,36(4):72-75.
[11]董林娟,张文娟,刘诗雨,等.龙脉宁方中葛根素在心肌缺血大鼠体内药动学-药效学相关性研究[J].中国中药杂志,2016,41(8):1535-1540.
[12]陈小新,原素,李耿,等.葛根素自微乳在Beagle犬体内的药代动力学及生物利用度研究[J].中药材,2011,34(5):750-753.
[13]杜力军,邢东明,炎彬,等.对葛根素与葛根黄酮体内动力学关系的探讨[J].世界科学技术-中医药现代化,2004,6(6):32.
[14]郭宇洁,孟硕,徐辉,等.葛根素和葛根黄酮的药代动力学研究概述[J].中国实验方剂学杂志,2009,15(6):82-85.
[15]崔升淼,赵春顺,毛晶晶,等.乳糖酸红霉素对葛根素药物动力学的影响[J].沈阳药科大学学报,2004,21(6):412-415
[16]赵延礼,潘振宇,于本涛.HPLC法测定大鼠血浆中葛根素含量[J].青海医药杂志,2009,39(4):59-60.