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醋酸艾塞那肽在Wistar大鼠体内的药物代谢动力学研究

艾国, 陈知航, 单成启, 车津晶, 侯禹男, 程远国*   

  1. 军事医学科学院 微生物流行病研究所 药物代谢动力学实验室, 北京 100071
  • 收稿日期:2007-06-18 修回日期:2008-01-10 出版日期:2008-03-15 发布日期:2008-03-15
  • 通讯作者: 程远国*

Pharmacokinetics of exendin-4 in Wistar rats

Guo Ai, Zhi-Hang Chen, Cheng-Qi Shan, Jin-Jing Che, Yu-Nan Hou, Yuan-Guo Cheng*   

  1. Laboratory of Drug Metabolism and Pharmacokinetics, Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, China
  • Received:2007-06-18 Revised:2008-01-10 Online:2008-03-15 Published:2008-03-15
  • Contact: Yuan-Guo Cheng*

摘要:

研究醋酸艾塞那肽(exendin-4)Wistar大鼠体内的药物代谢动力学, 组织分布以及排泄特征。IODOGEN(四氯二苯基苷脲)法制备125I-exendin-4, 大鼠皮下或静脉注射125I-exendin-4, 以放射性核素示踪动力法检测血液中的药物浓度, 由非房室模型评价药物动力学参数。同时研究了大鼠皮下注射125I-exendin-4后的组织分布和排泄。大鼠皮下注射125I-exendin-4Tmaxt1/2分别是(0.25 ± 0.02) h(1.28 ± 0.14) h, 绝对生物利用度为(65.5 ± 10.2) %; 125I-exendin-4的分布快速而广泛, 其中以肾脏中最高, 而在脑组织中只有微量125I-exendin-4; 125I-exendin-4主要随尿液排泄。实验结果与国外公布的实验数据基本一致。醋酸艾塞那肽在大鼠中的药物代谢动力学参数为临床试验提供了科学依据。

关键词: 醋酸艾塞那肽, 醋酸艾塞那肽, 醋酸艾塞那肽, 碘标记, 碘标记, 碘标记, 药物代谢动力学, 药物代谢动力学, 药物代谢动力学

Abstract:

To characterize the preclinical pharmacokinetics, tissue distribution and excretion profiles of exendin-4 in healthy Wistar rats were studied. Exendin-4 was radioiodinated by the IODOGEN (1,3,4,6-tetrachloro-3 alpha, 6 alphadiphenylglucoluril) method. Pharmacokinetic properties of 125I-exendin-4 were examined after a single s.c. and i.v. injection, respectively. Tissue distribution and urinary, fecal, and biliary excretion patterns of 125I-exendin-4 were also investigated following a single s.c. injection. Exendin-4 was rapidly distributed and cleared with t1/2 of (0.48 ± 0.03) h after a single i.v. injection. Following a single s.c. administration, exendin-4 exhibited rapid and considerable absorption with Tmax of (0.25 ± 0.02) h and declined with the elimination t1/2 of (1.28 ± 0.14) h. The absolute bioavailability was (65.5 ± 10.2) %. The radioactivity was widely distributed and rapidly diminished in most tissues. The kidney contained the highest radioactivity and the distribution of 125I-exendin-4 to the brain was minimal. The major elimination route was urinary excretion. The pharmacokinetic properties of exendin-4 obtained from the present study closely matched those reported in previous studies in rats. Pharmacokinetics profiles of exendin-4 in rats are warranted for the design of future clinical trials.

Key words: Exendin-4, Exendin-4, Iodine, Iodine, Pharmacokinetics, Pharmacokinetics

中图分类号: 

Supporting: Foundation item: National High Technology 863 Project (Grant No. 2003AA2Z347B).
*Corresponding author. Tel.: 86-10-66948493