目的 建立Beagle犬体内蝙蝠葛苏林碱(DS)和蝙蝠葛碱(Dau)的药动学-药效学(PK-PD)结合模型。方法 通过测定给药后Beagle犬体内的血药浓度并以给药后的Q-Tc间期延长率作为效应指标,采用Sheiner等提出的PK-PD结合模型进行PK-PD结合研究。结果 药物效应与效应室浓度成良好的相关性,符合Sigmoid-Emax模型,并通过计算得出相应的PK-PD模型参数。结论 本试验在Beagle犬体内成功地建立了DS和Dau的PK-PD结合模型,建立了药物效应E,血药浓度Cp及时间t之间的关系,故可较为成功地预测DS和Dau的血药浓度及其效应。
Abstract
OBJECTIVE To establish the pharmacokinetic-pharmacodynamic (PK-PD) characteristics of daurisoline (DS) and dauricine (Dau) in Beagle dogs. METHODS The plasma concentrations of DS and Dau were determined and the prolongation percentage of Q-Tc interval was observed as the effect index. The Sigmoid-Emax model was used to analyze the relationship among the plasma concentrations, time and effects of DS and Dau. RESULTS The relationship between effect and plasma concentration met the Sigmoid Emax model and the model parameter (Ke0 , Emax, EC50,γ) were calculated. CONCLUSION The PK-PD model of DS and Dau and the relationship among the effect, plasma concentration and time are established successfully.
关键词
蝙蝠葛苏林碱 /
蝙蝠葛碱 /
药动学-药效学结合模型
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Key words
daurisoline /
dauricine /
pharmacokinetic-pharmacodynamic linked model
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参考文献
[1]Sheiner LB.Stanski DR.Vozeh S,et al.Simultaneous modeling of pharmacokinetic and pharmacodynamics: application to D-tubocurarine[J].Clin Pharmacol Ther,1979,25(3):358.
[2]Holford NHG.Sheiner LB Understanding the dose-effect relationship: clinical application of pharmacokinetics- pharmacodynamic models[J].Clin Pharmacol,1981,6(6):429.
[3]Holford NHG.Sheiner LB Kinetics of pharmacological response[J].Pharmacol Ther,1982,16:143.
[4]胡燕,胡国新,方达超,等.清醒大鼠血流动力学的实验方法[J].中国药理学通报,1986,2(5):61.
[5]任平,焦凯,李月彩,等.川芎嗪和/或阿魏酸对麻醉狗血流动力学的不同效应[J].第四军医大学学报,1999,20(9):797.
[6]Huang X.Zang YM.Wang YM,et al.Effects of tetramethylpyrazine phosphate and sodium ferulate alone and in combination on hemodynamics in anesthetized[J],Am J Chin Med,1996,24(2):169.
[7]Fuseau E.Sheiner LB Commentary: Simultaneous modeling of pharmacokinetics and pharmacodynamics with a nonparametric pharmacodynamic model[J].Clin Pharmacol Ther,1984,35(6):733.
[8]刘昌孝,顾以保,冯建林,等.常咯啉在实验性心律失常狗的药代动力学-药效动力学分析[J].药学学报,1996,31(9):666.
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脚注
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基金
湖北省科委基金课题(99191609)
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