中国药物警戒 ›› 2015, Vol. 12 ›› Issue (9): 522-525.

• 基础与临床研究 • 上一篇    下一篇

高压氧对小鼠体内盐酸二甲双胍药动学的影响

宋金波1, 宋丹丹2, 沈佳伟2, 周玮丽2, 褚菲菲2, 施红2, 邵贵强2, 曹秀琴2   

  1. 1.复旦大学附属上海市第五人民医院,上海 200240;
    2.上海市闵行区吴泾医院药剂科,上海 200241
  • 收稿日期:2015-08-05 修回日期:2015-12-07 出版日期:2015-09-08 发布日期:2015-12-07
  • 通讯作者: 曹秀琴,女,本科,副主任药师,药事管理与临床药学。E-mail:caoxqin@163.com
  • 作者简介:宋金波,男,本科,副主任药师,临床药学。

Effects of Hyperbaric Oxygen on the Pharmacokinetics of Metformin Hydrochloride in Mice

SONG Jin-bo1, SONG Dan-dan2, SHEN Jia-Wei2, ZHOU Wei-li2, CHU Fei-fei2, SHI Hong2, SHAO Gui-qiang2, CAO Xiu-qin2   

  1. 1.Fifth People's Hospital of Shanghai, Fudan University, Shanghai 200240, China;
    2.Wujing Hospital of Shanghai Minhang District, Shanghai 200241, China
  • Received:2015-08-05 Revised:2015-12-07 Online:2015-09-08 Published:2015-12-07

摘要: 目的 研究高压氧(HBO)对盐酸二甲双胍(MET)药代动力学的影响。方法 200只小鼠随机分成对照组104只,和高压氧组(HBO组)96只,2组均按150 mg·kg-1剂量单次灌服盐酸二甲双胍溶液。HBO组灌服后立即置于高压氧舱,稳压(0.20 MPa)吸纯氧20 min,升压、减压各5 min;对照组仅单次灌服盐酸二甲双胍溶液。2组在给药前及给药后不同时间点各取8只小鼠,球后静脉丛取血,采用高效液相色谱法测定血浆中MET的浓度,计算药代动力学参数。结果HBO组峰浓度(Cmax)、达峰时间(tmax)、血浆半衰期(t1/2)、平均血药浓度一时间曲线下面积(AUC)、清除率(CL/F)和表观分布容积(Vd)分别为:(9.64±2.94)μg·mL-1、(0.42±0.12) h、(5.28±0.78) h、(29.76±5.21)μg·h·mL-1、(4.94±0.65) L·h-1·kg-1、(12.46±3.17) L·kg-1;对照组分别为:(18.68±4.26)μg·mL-1、(0.10±0.04)h、(7.41±1.06) h、(44.12±7.15)μg·h·mL-1、(3.32±0.63)L·h-1·kg-1、(7.62±1.97) L·kg-1。结论 HBO可以明显加快小鼠体内MET的消除,对药代动力学参数有明显的影响。

关键词: 高压氧, 盐酸二甲双胍, 药代动力学, 高效液相色谱法

Abstract: Objective To investigate the effects of hyperbaric oxygen(HBO)on the pharmacokinetics of MET. Methods Two hundred mice were randomly divided into 2 groups, the HBO group and the control group. The 2 groups of animals received gavage of MET with a single-dose of 150 mg·kg-1. The animals in the HBO group were immediately put into the hyperbaric oxygen chamber and maintained at a pressure of 0.20 MPa for a duration of 20 min. The time used for compression and decompression was both 5 min. The animals in the control group were just given a single gavage of MET. Eight animals from each group were chosen at different time points both before and after drug administration, for collection of blood samples from the eyeballs. Concentrations of MET in serum were monitored with high performance liquid chromatography, and pharmacokinetic indices were calculated accordingly. Results The main pharmaeokinetic parameters of the HBO group were as follows: Cmax(9.64±2.94)μg·mL-1, tmax(0.42±0.12)h, t1/2 (5.28±0.78)h, AUC(29.76±5.21)μg·mL-1·h, CL/F (4.94±0.65)L·h-1·kg-1, Vd (12.46±3.17)L·kg-1, while the corresponding results of the control group were Cmax (18.68±4.26)μg·mL-1, tmax (0.10±0.04)h, t1/2 (7.41±1.06)h, AUC(44.12±7.15)μg·mL-1·h, CL/F (3.32±0.63)L·h-1·kg-1, Vd (7.62±1.97)L·kg-1. Conclusion HBO could obviously accelerate the elimination of MET and seemed to have significant effect on pharmacokinetic parameters.

Key words: hyperbaric oxygen, metformin hydrochloride, pharmacokinetics, HPLC

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