蝙蝠葛苏林碱和蝙蝠葛碱犬体内药动学-药效学结合研究

Study on the pharmacokinetic-pharmacodynamic characteristics of daurisoline and dauricine in Beagle dogs

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。

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 (K β0, 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.