中国药物警戒 ›› 2019, Vol. 16 ›› Issue (10): 577-580.
DOI: 10.19803/j.1672-8629.2019.10.01

• 基础与临床研究 •    下一篇

异补骨脂素重复给药3个月在大鼠体内的毒代动力学研究

门伟婕1, 霍香香1, 毕亚男1, 袁晓美1, 张玥1, 2, *, 周昆1, 2   

  1. 1 天津中医药大学中医药研究院,天津300193;
    2 天津市中药药理学重点实验室,天津 300193
  • 收稿日期:2019-10-24 修回日期:2019-10-24 出版日期:2019-10-20 发布日期:2019-10-24
  • 通讯作者: 张玥,女,博士,实验师,中药药理毒理研究。E-mail:zhangyue@tjutcm.edu.cn
  • 作者简介:门伟婕,女,在读硕士,中药药理毒理研究。
  • 基金资助:
    国家自然科学基金面上项目（81673826）：一种基于靶器官效应和分布的中药毒效成分评价方法及其在补骨脂毒性物质基础研究中的应用; 国家重大新药创制专项（2014ZX09304307-001-005）:中药新药安全性检测技术与标准研究

Pharmacokinetics of Isopsoralen in Rat Model with 3 Months of Repeated Administration

MEN Weijie1, HUO Xiangxiang1, BI Yanan1, YUAN Xiaomei1, ZHANG Yue1, 2, *, ZHOU Kun1, 2   

  1. 1 Institute of Traditional Chinese Medicine,Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China;
    2 Tianjin Key Laboratory of Chinese Medicine Pharmacology, Tianjin 300139, China
  • Received:2019-10-24 Revised:2019-10-24 Online:2019-10-20 Published:2019-10-24

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摘要： 目的 研究异补骨脂素重复给药3个月大鼠体内的药代动力学。方法 Wistar大鼠36只,雌雄各半,随机分为3组,分别给予14.0、7.0、3.5 mg·kg-1的异补骨脂素（高、中、低剂量组）,连续灌胃给药3个月,每天给药1次,分别在末次灌胃的给药前及给药后取血测定不同时间点大鼠血浆中的异补骨脂素浓度,用DAS 3.0程序计算药物动力学参数。结果 高、中、低3个剂量组的异补骨脂素重复灌胃给药后在大鼠体内的药代动力学参数显示：AUC分别为：（27287.42±2680.24）、（18483.87±2455.46）、（5189.97±791.67）μg·L-1·h-1;t1/2分别为：(4.67±0.80）、（11.30±2.37）、（5.87±1.52）h;Cmax分别是（2509.26±191.78）、（2287.06±172.43）、（825.64±76.45）μg·L-1。大鼠体内的AUC、Cmax与MRT随剂量的升高而升高。结论 在本研究剂量范围内(3.5 ~14.0 mg·kg-1 ),异补骨脂素重复灌胃给药在大鼠体内的药代过程属于非线性药代动力学。

关键词: 药代动力学, 异补骨脂素, 高效液相色谱法, 重复给药

Abstract: Objective To study the pharmacokinetics of isopsoralen after 3 months of repeated administration in rats. Methods Thirty-six Wistar rats (half male and half female) were randomly divided into three groups. Isopsoralen (14.0, 7.0, 3.5 mg·kg-1) was given for 3 months by continuous gavage , once a day. Blood samples were taken before and after the last gavage to determine the plasma concentration of isopsoralen in rats at different time points, and the pharmacokinetic parameters were calculated with DAS3.0 program. Results The pharmacokinetic parameters of isopsoralen in rats after repeated gavage in high, medium and low dose groups were as follows: AUC was（27287.42±2680.24）,（18483.87±2455.46）and（5189.97±791.67）μg·L-1·h-1 respectively, t1/2 was (4.67±0.80）,（11.30±2.37）and（5.87±1.52）h respectively, while Cmax was（2509.26±191.78）,（2287.06±172.43）and（825.64±76.45）μg·L-1 respectively. AUC, Cmax and MRT in rats increased with the dose. Conclusion Within the dose range of this study (3.5-14.0 mg·kg-1), the pharmacokinetics of isopsoralen given by repeated gavage in rats is nonlinear.

Key words: pharmacokinetics, isopsoralen, high performance liquid chromatography, repeated dosing

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