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大黄及牛黄解毒片大鼠给药后血浆中大黄活性成分的药代动力学比较研究

刘玥昕, 吴骁, 关蓉, 杭太俊, 宋敏

刘玥昕, 吴骁, 关蓉, 杭太俊, 宋敏. 大黄及牛黄解毒片大鼠给药后血浆中大黄活性成分的药代动力学比较研究[J]. 中国药科大学学报, 2018, 49(4): 449-455. DOI: 10.11665/j.issn.1000-5048.20180410
引用本文: 刘玥昕, 吴骁, 关蓉, 杭太俊, 宋敏. 大黄及牛黄解毒片大鼠给药后血浆中大黄活性成分的药代动力学比较研究[J]. 中国药科大学学报, 2018, 49(4): 449-455. DOI: 10.11665/j.issn.1000-5048.20180410
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LIU Yuexin, WU Xiao, GUAN Rong, HANG Taijun, SONG Min. Comparative pharmacokinetics of active anthraquinones ingredients after oral administration of Rhei Radix et Rhizoma and Niuhuang Jiedu Tablets to rats[J]. Journal of China Pharmaceutical University, 2018, 49(4): 449-455. DOI: 10.11665/j.issn.1000-5048.20180410
Citation: LIU Yuexin, WU Xiao, GUAN Rong, HANG Taijun, SONG Min. Comparative pharmacokinetics of active anthraquinones ingredients after oral administration of Rhei Radix et Rhizoma and Niuhuang Jiedu Tablets to rats[J]. Journal of China Pharmaceutical University, 2018, 49(4): 449-455. DOI: 10.11665/j.issn.1000-5048.20180410
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大黄及牛黄解毒片大鼠给药后血浆中大黄活性成分的药代动力学比较研究

  • 中国药科大学药物分析系

基金项目: 国家自然科学基金资助项目(No.81173648)

Comparative pharmacokinetics of active anthraquinones ingredients after oral administration of Rhei Radix et Rhizoma and Niuhuang Jiedu Tablets to rats

摘要

    摘要
  • 摘要: 考察大黄及牛黄解毒片给药后大黄活性成分在大鼠体内药代动力学行为的差异。大鼠分别灌胃给予大黄生药材96 mg/kg(含总蒽醌1.83 mg/kg，相当于大黄酸0.28 mg/kg、大黄素0.30 mg/kg、大黄酚0.81 mg/kg、芦荟大黄素0.23 mg/kg及大黄素甲醚0.20 mg/kg)及牛黄解毒片250 mg/kg(含总蒽醌与大黄生药材等量，相当于大黄酸0.33 mg/kg、大黄素0.38 mg/kg、大黄酚0.71 mg/kg、芦荟大黄素0.24 mg/kg及大黄素甲醚0.17 mg/kg)，血浆经甲醇沉淀后，采用LC-MS/MS法测定大黄活性成分血药浓度，WinNonlin 7.0软件计算药代动力学参数。大鼠灌胃大黄及牛黄解毒片后，大黄酸的cmax分别为(121±103)及(474±251)μg/L，AUC0-t分别为(275±176)及(406±194)μg·h/L；大黄酚异构体的cmax分别为(2 325±1 390)及(3 580±2 169)μg/L，AUC0-t分别为(8 170±2 661)及(8 856±4 023)μg·h/L；仅在牛黄解毒片给药大鼠血浆中检测出大黄素，且牛黄解毒片给药后大鼠血浆中大黄酸的cmax、AUC及t1/2，大黄酚异构体的Vd及CL与单味大黄相比显著增加，大黄酚异构体的tmax显著下降。实验结果表明，牛黄解毒片复方配伍增强了大黄活性成分在大鼠体内的吸收利用，改变了大黄活性成分的药代动力学行为。
    Abstract: The study aims to investigate different pharmacokinetic profilesof anthraquinones after oral administration of Rhei Radix et Rhizoma and Niuhuang Jiedu Tablets(NHJDT)in rats, respectively. Rats were administrated with 96 mg/kg of Rhei Radix et Rhizoma(1. 83 mg/kg of total anthraquinone, equivalent to 0. 28 mg/kg of rhein, 0. 30 mg/kg of emodin, 0. 81 mg/kg of chrysophanol, 0. 23 mg/kg of aloe-emodin and 0. 20 mg/kg of physcion)or 250 mg/kg of NHJDT(equal dose of total anthraquinone as Rhei Radix et Rhizoma, equivalent to 0. 33 mg/kg of rhein, 0. 38 mg/kg of emodin, 0. 71 mg/kg of chrysophanol, 0. 24 mg/kg of aloe-emodin and 0. 17 mg/kg of physcion), respectively. Followed by protein precipitation with methanol, the anthraquinones in plasma samples were determined by LC-MS/MS. The pharmacokinetic parameters were calculated by WinNonlin 7. 0. The cmaxof rhein were(121±103)and(474±251)μg/L, and the AUC0-twere(275±176)and(406±194)μg ·h/L for Rhei Radix et Rhizoma and NHJDT, respectively. The cmaxof chrysophanol isomer were(2 325±1 390)and(3 580±2 169)μg/L, and the AUC0-twere(8 170±2 661)and(8 856±4 023)μg ·h/L, respectively. Emodin in very low levels was only detected in rat plasma samples after oral gavage of NHJDT. The cmax, AUC and t1/2 of rhein, as well as Vd and CL of chrysophanol isomer were observed with a much increased degree in comparison with Rhei Radix et Rhizoma counterparts. However, much shorter tmaxwas found in NHJDT group. Therefore, NHJDT with co-existing components enhanced the absorption and influenced the pharmacokinetic behaviors of active ingredients in Rhei Radix et Rhizoma.
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    • 参考文献(15)
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  • 刊出日期:  2018-08-24

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