蝙蝠葛苏林碱在兔体内的药代动力学及组织分布

目的:研究蝙蝠葛苏林碱(DS)在兔体内的药代动力学和组织分布特征.方法:兔耳缘静脉注射给予DS后,采用高效液相色谱法测定各时间点血浆和组织器官药物浓度,并用3p97程序计算药代动力学参数.结果:兔DS 2.5、5、10 mg·kg-1静脉注射给药后,体内动力学行为符合二房室开放模型.T1/2β分别为 3.0±0.6、3.4±0.9 和 6.9±0.6 h;Cls分别为 3.1±0.6、3.6±0.4 和 4.4±0.3 L·h·kg-1;Vd分别为 13.1±2.7、18.0±6.2 和 43.6±4.4 L·kg-1;AUC0～t分别为 0.84±0.13、1.41±0.17 和 2.30±0.18 mg·h·L-1.在DS 2.5～5 mg·kg-1范围内主要药动学参数无显著性差异(P>0.05),但DS 10 mg·kg-1静脉注射后,C0超比例增加(P＜0.01),T1/2β明显延长(P＜0.01).结论:在 2.5～5 mg·kg-1范围内DS的消除为线性动力学,而10 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,其次为肾、脾和肝脏.各组织器官中药量均显著高于血浆药物浓度.

Pharmacokinetics and tissue distribution of daurisoline in rabbits

AIM: To investigate the pharmacokinetics and tissue distribution of daurisoline (DS) after administration in rabbits. METHODS: Single dose concentrations in plasma and tissues were measured by a validated high performance liquid chromatography method. RESULTS: Plasma concentration-time profiles were adequately described by a two-compartment open model. The main pharmacokinetic parameters after iv DS 2.5, 5 and 10 mg·kg-1 were as follows: T1/2β were 3.0±0.6, 3.4±0.9 and 6.9±0.6 h, respectively,Cls were 3.1±0.6, 3.6±0.4 and 4.4±0.3 L·h·kg-1, respectively,Vd were 13.1±2.7, 18.0±6.2 and 43.6±4.4 L·kg-1, respectively,and AUC0～t were 0.84±0.13, 1.41±0.17 and 2.30±0.18 mg·h·L-1, respectively. At dosages of 2.5 and 5 mg·kg-1, no statistically significant difference existed in main pharmacokinetic parameters. However, T1/2β and C0 increased nonproportionally when the dosage was 10 linear kinetics. However, a nonlinear kinetics is found at dosage of 10 distribution to the lung, kidney, spleen, and liver, and displays substantial penetration into tissues.