蝙蝠葛苏林碱在犬体内药动学-药效学结合模型研究

Pharmacokinetic-pharmacodynamic modeling of daurisoline in beagle dogs

目的 :研究蝙蝠葛苏林碱在beagle犬体内的药动学与药效学之间的关系。 方法 :4只beagle犬给予蝙蝠葛苏林碱 6mg·kg-1静脉注射后 ,分时取血 ,同时通过生理记录仪观察犬心电、血压及血流动力学的变化。采用反相高效液相色谱法测定血浆中蝙蝠葛苏林碱的浓度。结果 :蝙蝠葛苏林碱在犬体内动力学行为符合二房室开放模型 ,对犬药效学影响峰值为 10～ 15min ,皆明显滞后于血药浓度峰值。结论 :通过在beagle犬体内建立的蝙蝠葛苏林碱药动学 药效学 (PK PD)结合模型 ,可以成功预测蝙蝠葛苏林碱的血药浓度及其药理效应。

OBJECTIVE To investigate the relationship between pharmacokinetics and pharmacodynamics of daurisoline (DS) in beagle dogs.METHODS The blood was drawn at intervals and the cardiac electrophsiology,blood pressure and hemodynamics were recorded by polygraph after iv DS 6 mg·kg -1 in beagle dogs.The plasma drug concentration was determined by the reversed-phase HPLC.RESULTS The pharmacokinetics were best fitted to a two-compartment open model.The maximum pharmacological effects of DS were 10～15 min later than the maximum plasma concentrations.CONCLUSIONS A combinded PK-PD modeling was developed to predict successfully the plasma concentration and pharmacological effects of DS in beagle dogs.