摘要
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DS2.5、5、10mg·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。T12β分别为3.0±0.6、3.4±0.9和6.9±0.6h;Cls分别为3.1±0.6、3.6±0.4和4.4±0.3L·h·kg-1;Vd分别为13.1±2.7、18.0±6.2和43.6±4.4L·kg-1;AUC0～t分别为0.84±0.13、1.41±0.17和2.30±0.18mg·h·L-1。在DS2.5～5mg·kg-1范围内主要药动学参数无显著性差异(P>0.05),但DS10mg·kg-1静脉注射后,C0超比例增加(P<0.01),T12β明显延长(P<0.01)。结论:在2.5～5mg·kg-1范围内DS的消除为线性动力学,而10mg·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。
AIM: To investigate the pharmacokinetics and tissue distribution of daurisoline (DS) after administration in rabbits. METHODS: Single dose of 2.5, 5 or 10 mg·kg -1 DS of body weight was administrated in rabbits. The tissue distribution of DS (10 mg·kg -1) was investigated, and the 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: T_ 1/2β 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,V_d were 13.1± 2.7, 18.0± 6.2 and 43.6± 4.4 L·kg -1, respectively,and AUC_ 0～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, T_ 1/2β and C_0 increased nonproportionally when the dosage was 10 mg·kg -1. CONCLUSION: Across the dosages of 2.5-5 mg·kg -1, DS demonstrates linear kinetics. However, a nonlinear kinetics is found at dosage of 10 mg·kg -1. Assessment of tissue concentrations of DS reveals preferential distribution to the lung, kidney, spleen, and liver, and displays substantial penetration into tissues.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2005年第6期622-626,共5页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
ProjectSupportedbytheScientificResearchFoundationofCommitteeofScienceandTechnologyofHubeiProvince(№991P1609)
关键词
蝙蝠葛苏林碱
高效液相色谱法
药代动力学
组织分布
daurisoline
high performance liquid chromatography
pharmacokinetics
tissue distribution
