目的研究蝙蝠葛苏林碱(DS)在兔体内的药动学和组织分布特征。方法兔耳缘静脉注射DS后,采用HPLC测定各时间点血浆和组织器官药物浓度。结果兔DS 2.5,5.0,10.0 mg·kg^-1静脉注射后,体内动力学行为符合二室开放模型。t_1/2α分别为0.024,0.030,0.018 h;t_1/2β分别为3.0,3.4,6.9 h;CL分别为3.1,3.6,4.4 L·kg^-1·h^-1;Vd分别为13.1,18.0,43.6L·kg^-1。在DS 2.5～5.0 mg·kg^-1内主要药动学参数无显著性差异(P>0.05),但DS 10.0 mg·kg^-1静脉注射后,ρ₀超比例增加(由2.08 mg·L^-1增加至10.72 mg·L^-1,P<0.01),t_1/2β明显延长(P<0.01)。结论DS在兔体内分布迅速、广泛,消除较快。在2.5～5.0 mg·kg^-1内DS的消除为线性动力学,而10.0 mg·kg^-1静脉注射后,本品在兔体内的消除未呈线性动力学。组织分布以肺脏含量最高,各组织器官中药量均显著高于血浆药物浓度。

OBJECTIVE To investigate the pharmacokinetics and distribution of daurisoline in rabbits.METHODS The plasma and tissue concentrations of DS were determined by reversed phase HPLC method after intravenous bolus doses of 2.5,5.0 and 10.0 mg·kg^-1.RESULTS The concentration-time profile was discribed by a 2-compartment open model.The main pharmacokinetic parameters of the three doses were: t_1/2α0.024,0.030 and 0.018 h,t_1/2β 3.0,3.4 and 6.9 h,CL 3.1,3.6 and 4.4 L·kg^-1·h^-1,Vd 13.1,18.0 and 43.6 L·kg^-1.At the dosages of 2.5 and 5.0 mg·kg-1,there was no statistically significant difference in the main pharmacokinetic parameters.However,ρ₀ and t_1/2β were increased out of proportion when the dosage was 10.0 mg·kg^-1.CONCLUSION At the dosages of 2.5 and 5.0 mg·kg^-1,the elimination of DS from the plasma was found to be in accord with linear kinetics,when the dosage was 10.0 mg·kg^-1,a non-linear kinetics was observed.DS was distributed quickly and extensively,the highest level of the drug was found in the lung and the concentrations in all tissues were higher than that in plasma.