急进高原对米格列醇在大鼠体内药代动力学参数的影响  

Effects of Acute Exposure to High Altitude on Pharmacokinetic Parameters of Miglitol in Rats

作　　者：张晓静 黄隆基 牟宏芳 王荣 ZHANG Xiaojing;HUANG Longji;MU Hongfang;WANG Rong(Department of Pharmacy,NO.940 Hospital of Joint Logistics Support Force of People′s Liberation Army,Lanzhou Gansu 730050,China)

机构地区：[1]联勤保障部队940医院药剂科,甘肃兰州730050

出　　处：《联勤军事医学》2023年第8期643-646,702,共5页Military Medicine of Joint Logistics

基　　金：甘肃省科技计划资助项目(22JR5RA017)。

摘　　要：目的探讨急进高原后高原环境对米格列醇在Wistar大鼠体内药代动力学参数的影响。方法将12只大鼠随机分为平原组与高原组,两组大鼠分别给予5.25 mg/kg米格列醇灌胃,并分别于给药后5、10、15、30、60、90、120、240 min眼眶静脉丛采集血样。液相色谱-串联质谱法(liquid chromatography tandem mass spectrometry,LC-MS/MS)测定大鼠血浆中米格列醇浓度,采用WinNonlin 8.1软件计算药代动力学参数。结果LC-MS/MS测定米格列醇血浆浓度在一定浓度范围内线性关系良好(r=0.996),日内精密度和日间精密度均小于10%且稳定性良好。与平原组大鼠相比,米格列醇在高原组大鼠体内的达峰血药浓度增加、平均滞留时间延长、半衰期延长、清除率减小、曲线下面积(area under the curve,AUC)增加(P均<0.05)。结论急进高原后,米格列醇在大鼠体内吸收增加、代谢减慢,为进一步研究糖尿病患者高原环境下合理用药提供参考。Objective To investigate the effects of high altitude environment on the pharmacokinetic parameters of miglitol in Wistar rats after acute exposure to high altitude.Methods A total of 12 rats were randomly divided into plain group and high altitude group,blood samples were collected from veins of eye sockets at 5,10,15,30,60,90,120 and 240 minutes after intragastric administration of 5.25 mg/kg miglitol in both groups of rats.Liquid chromatography tandem mass spectrometry(LC-MS/MS)was used to determine the concentration of miglitol in plasma of rats,and the pharmacokinetic parameters were calculated by WinNonlin 8.1 software.Results The plasma concentration of miglitol measured by LC-MS/MS had good correlation coefficient within a certain concentration range(r=0.996),and the intra-day relative standard deviation and inter-day relative standard deviation were less than10%and with good stability.Compared with the rats in plain group,the peak concentration of miglitol in the high altitude rats significantly increased,the mean residence time was extended,the half-life increased,the clearance rate decreased and the area under the curve(AUC)increased(all P<0.05).Conclusion The absorption of miglitol increases and the metabolism reduces in rats after acute exposure to high altitude,which provides a reference for further study of rational drug uses in diabetic patients under the high altitude environment.

关 键 词：高原环境 液相色谱-串联质谱 米格列醇 药代动力学参数 

分 类 号：R917[医药卫生—药物分析学]