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生脉注射液中人参皂苷Rg1,Rb1在心肌缺血大鼠体内的药动学-药效学结合研究

Keywords: 生脉注射液,人参皂苷Rg1,人参皂苷Rb1,一氧化氮,药动学-药效学结合

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Abstract:

该文研究生脉注射液中主要成分人参皂苷Rg1和Rb1在心肌缺血大鼠体内的药动学过程及其诱导体内NO释放效应的药动学-药效学(PK-PD)结合模型。以大鼠皮下注射异丙肾上腺素(ISO)制备心肌缺血模型。模型大鼠静脉给予生脉注射液(10.8mL·kg-1),于给药后不同时间点采集大鼠血清,测定血清中人参皂苷Rg1和Rb1的浓度,绘制药-时曲线,拟合药动学模型,计算药动学参数;同时测定血清中NO代谢产物NO2-和NO3-水平,绘制时-效曲线,采用Sheiner等提出的效应室理论建立PK-PD结合模型,计算药效学参数。研究结果显示人参皂苷Rg1和Rb1在大鼠体内的药动学过程均符合二房室开放模型,人参皂苷Rg1在体内表现出快消除的特点,人参皂苷Rb1表现出慢消除的特点。生脉注射液诱导大鼠体内NO释放效应与人参皂苷Rg1和Rb1的血药浓度不直接相关,效应滞后于血药浓度,效应与人参皂苷Rg1和Rb1的效应室浓度成良好的相关性,符合Sigmoid-Emax模型。该研究成功建立了生脉注射液在心肌缺血大鼠体内的PK-PD结合模型,可较有效地用于预测生脉注射液的血药浓度和效应。

References

[1]  Abdel-Rahman S M, Kauffman R E. The integration of pharmacokinetics and pharmacodynamics: understanding dose-response [J]. Annu Rev Pharmacol Toxicol, 2004, 44:111.
[2]  Csajka C, Verotta D. Pharmacokinetic-pharmacodynamic modelling: history and perspectives[J]. J Pharmacokinet Pharmacodyn, 2006, 33(3): 227.
[3]  袁美燕,吴虹. PK-PD 模型在中药药物代谢动力学中的应用[J].安徽中医学院学报,2009,28(5): 86.
[4]  曹岗,张云,丛晓东,等. PK-PD模型在中药药动学中的应用[J].中草药,2009,40(11): 1830.
[5]  陈琼,冬雪川,师少军,等.蝙蝠葛苏林碱和蝙蝠葛碱犬体内药动学-药效学结合研究 [J].中国药学杂志,2004,39(5): 366.
[6]  Chen J, Yao Y, Chen H,et al. Shengmai(a traditional Chinese herbal medicine)for heart failure [J]. Cochrane Database Syst Rev, 2012, 11:CD005052.
[7]  石蓓佳, 吴莉. 生脉注射液在家兔体内的药代动力学研究[J]. 中成药, 2009, 31(4): 653.
[8]  李国信, 唐思, 夏素霞, 等. 生脉拆方系列注射液中人参皂苷Rg1和Re 药代动力学研究[J]. 中华中医药学刊, 2010, 28(11): 2310.
[9]  姜春梅, 李国信, 夏素霞, 等. 生脉注射液中人参皂苷Rb1在健康人体的药动学[J]. 中国新药杂志, 2011, 20(9): 803.
[10]  Han M, Fu S, Fang X L. Comparison between the characteristics of absorption and pharmacokinetic behavior of ginsenoside Rg1 and ginsenoside Rb, of Panax notoginseng saponins[J]. Acta Pharm Sin, 2007, 42(8): 849.
[11]  Liu H, Yang J, Du F,et al. Absorption and disposition of ginsenosides after oral administration of Panax notoginseng extract to rats[J]. Drug Metab Dispos, 2009, 37(12): 2290.
[12]  Sheiner L B, Steimer J L. Pharmacokinetic/pharmacodynamic modeling in drug development[J]. Annu Rev Pharmacol Toxicol, 2000, 40: 67.
[13]  Derendorf H, Lesko L J, Chaikin P,et al. Pharmacokinetic/pharmacodynamic modeling in drug research and development [J]. J Clin Pharmacol, 2000, 40(12 Pt 2): 1399.
[14]  Leung K W, Cheng Y K, Mak N K, et al. Signaling pathway of ginsenoside-Rg1 leading to nitric oxide production in endothelial cells[J]. FEBS Lett, 2006, 580(13): 3211.
[15]  Yu J, Eto M, Akishita M, et al. Signaling pathway of nitric oxide production induced by ginsenoside Rb1 in human aortic endothelial cells: a possible involvement of androgen receptor[J]. Biochem Biophysi Res Communic, 2007, 353(3): 764.
[16]  Leung K W, Leung F P, Mak N K,et al. Protopanaxadiol and protopanaxatriol bind to glucocorticoid and oestrogen receptors in endothelial cells[J]. Br J Pharmacol, 2009, 156(4): 626.
[17]  Pan C, Huo Y, An X,et al. Panax notoginseng and its components decreased hypertension via stimulation of endothelial-dependent vessel dilatation[J]. Vascul Pharmacol, 2012, 56(3/4): 150.
[18]  Chu K M, Hu O Y, Shieh S M. Cardiovascular effect and simultaneous pharmacokinetic and pharmacodynamic modeling of pimobendan in healthy normal subjects[J]. Drug Metab Dispos, 1999, 27(6): 701.
[19]  Liu X Y, Wang B J, Yuan G Y,et al. Comparison of different pharmacodynamic models for pharmacokinetic-pharmacodynamic(PK-PD)modeling of carvedilol[J]. Acta Pharm Sin, 2009, 44(4): 406.
[20]  师少军,顾世芬,陈汇,等.蝙蝠葛碱在犬体内的药代动力学和药效动力学研究[J].中国药理学通报,2005,21(4): 464.
[21]  Sheiner L B, Stanski D R, Vozeh S, et al. Simultaneous modeling of pharmacokinetics and pharmacodynamics: application to d-tubocurarine[J]. Clin Pharmacol Ther, 1979, 25(3): 358.
[22]  Holford N H, Sheiner L B. Understanding the dose-effect relationship: clinical application of pharmacokinetic-pharmacodynamic models [J]. Clin Pharmacokinet, 1981, 6(6): 429.
[23]  郭文婧. 生脉方药代动力学研究[D]. 杭州:浙江大学,2012.
[24]  Zhan S Y, Shao Q, Liu L,et al. A simple and accurate method to determine nitrite and nitrate in serum based on high-performance liquid chromatography with fluorescence detection[J]. Biomed Chromatogr, 2013, 27(11): 1547.
[25]  Xu Q F, Fang X L, Chen D F. Pharmacokinetics and bioavailability of ginsenoside Rb1 and Rg1 from Panax notoginseng in rats[J]. J Ethnopharmacol, 2003, 84(2/3): 187.

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