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中国临床药理学与治疗学 ›› 2005, Vol. 10 ›› Issue (6): 622-626.

• 研究原著 • 上一篇    下一篇

蝙蝠葛苏林碱在兔体内的药代动力学及组织分布

师少军, 李忠芳1, 顾世芬2, 陈汇2, 曾繁典2   

  1. 同济医学院附属协和医院药剂科, 1妇产科, 武汉430022, 湖北;
    2华中科技大学同济医学院临床药理研究所, 武汉430030, 湖北
  • 收稿日期:2005-04-27 修回日期:2005-06-02 出版日期:2005-06-26 发布日期:2020-11-12
  • 基金资助:
    Project Supported by the Scientific Research Foundation of Committee of Science and Technology of Hubei Province (NO991P1609)

Pharmacokinetics and tissue distribution of daurisoline in rabbits

SHI Shao-jun, LI Zhong-fang1, GU Shi-fen2, CHEN hui2, ZENG Fan-dian2   

  1. Department of Pharmacy, 1Department of Obstetrics and Gynecology, Xiehe Hospital Affiliated to Tongji Medical College, Wuhan 430022, Hubei, China;
    2Institute of Clinical Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China
  • Received:2005-04-27 Revised:2005-06-02 Online:2005-06-26 Published:2020-11-12
  • Contact: SHI Shao-jun, male, doctor of medicine, engaged in clinical pharmacology and cardiovascular pharmacology. Tel:027-85726073 E-mail: sjshicn@163.com
  • About author:ZENG Fan-dian, male, tutor of doctor, professor, engaged in clinical pharmacology and cardiovascular pharmacology.

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 ±4.4L·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DS10 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。

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

Abstract: 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 twocompartment 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 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.

Key words: daurisoline, high performance liquid chromatography, pharmacokinetics, tissue distribution

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