高压氧对小鼠体内盐酸二甲双胍药动学的影响  

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

作　　者：宋金波[1] 宋丹丹 沈佳伟 周玮丽 褚菲菲 施红 邵贵强 曹秀琴 

机构地区：[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

出　　处：《中国药物警戒》2015年第9期522-525,共4页Chinese Journal of Pharmacovigilance

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·m L-1、(0.42±0.12)h、(5.28±0.78)h、(29.76±5.21)μg·h·m L-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·m L-1、(0.10±0.04)h、(7.41±1.06)h、(44.12±7.15)μg·h·m L-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。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·h·mL-1、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.

关 键 词：高压氧 盐酸二甲双胍 药代动力学 高效液相色谱法 

分 类 号：R969.1[医药卫生—药理学] R977.15[医药卫生—药学]