Article(id=1236678241235300669, tenantId=1146029695717560320, journalId=1235980733773295621, issueId=1236678235866583092, articleNumber=null, orderNo=null, doi=null, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=null, receivedDateStr=null, revisedDate=null, revisedDateStr=null, acceptedDate=1661270400000, acceptedDateStr=2022-08-24, onlineDate=1772776669081, onlineDateStr=2026-03-06, pubDate=1688054400000, pubDateStr=2023-06-30, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1772776669081, onlineIssueDateStr=2026-03-06, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1772776669081, creator=13701087609, updateTime=1772776669081, updator=13701087609, issue=Issue{id=1236678235866583092, tenantId=1146029695717560320, journalId=1235980733773295621, year='2023', volume='32', issue='12', pageStart='1177', pageEnd='1280', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1772776667801, creator=13701087609, updateTime=1772776891082, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1236679172442092503, tenantId=1146029695717560320, journalId=1235980733773295621, issueId=1236678235866583092, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1236679172442092504, tenantId=1146029695717560320, journalId=1235980733773295621, issueId=1236678235866583092, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=1253, endPage=1258, ext={EN=ArticleExt(id=1236678241465987399, articleId=1236678241235300669, tenantId=1146029695717560320, journalId=1235980733773295621, language=EN, title=Effects of high-altitude hypoxia environment on pharmacokinetics of metformin after multiple administration in type 2 diabetes mellitus rats, columnId=null, journalTitle=Chinese Journal of New Drugs, columnName=null, runingTitle=null, highlight=null, articleAbstract=
Objective: To probe the effects of high-altitude hypoxia environment on the pharmacokinetic parameters of metformin after multiple administration in type 2 diabetes mellitus (T2DM) rats.
Methods: Liquid chromatography-mass spectrometry (LC-MS/MS) was used, separation was conducted by a Gemini C18 (75 mm×3 mm, 3 μm) column, the mobile phase was acetonitrile-water-formic acid (85∶15∶0.1, v/v/v), the flow rate was 0.4 mL·min-1, the injection volume was 2 μL, and the internal standard was ranitidine. T2DM rats were randomly divided into plain group and plateau group, and were given continuous gavage once a day for 7 days, and on the 7th day blood samples were collected before administration and at 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, 24 h after administration for determination of drug concentration. The DAS 2.0 software was used to simulate and fit the plasma concentration-time data to calculate the pharmacokinetic parameters.
Results: Compared with the rats in the plain group, the peak time (Tmax), clearance rate (CLZ/F) and average residence time (MRT) of metformin were prolonged by 29.03%, 33.25% and 44.98% (P<0.05) in the rats under high-altitude environment, respectively. The AUC increased by 46.22% (P<0.01).
Conclusion: The elimination of metformin is slowed down in T2DM rats after multiple administration under high-altitude hypoxia environment.
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目的： 探讨高原低氧环境对二甲双胍在2型糖尿病（type 2 diabetes mellitus, T2DM）大鼠体内多次给药后药动学参数的影响。
方法： 采用LC-MS/MS法，Gemini C18（75 mm×3 mm，3 μm）色谱柱进行分离，流动相为乙腈-水-甲酸（85∶15∶0.1，v/v/v），流速0.4 mL·min-1，进样量为2 μL，内标为雷尼替丁。12只T2DM大鼠随机分为平原组和高原组，连续灌胃给药二甲双胍7 d，qd，并于d 7给药前和给药后0.083，0.25，0.5，0.75，1，1.5，2，4，6，8，12，24 h采集血样进行检测，使用DAS 2.0软件对血药浓度-时间数据进行模拟拟合以计算药动学参数。
结果： 与平原组大鼠相比，高原低氧环境下大鼠体内二甲双胍的Tmax、清除率（CLZ/F）和平均滞留时间（MRT）分别延长了29.03%，33.25%和44.98%（P<0.05），同时AUC增加了46.22%（P<0.01）。
结论： 高原低氧环境下二甲双胍多次给药后在T2DM大鼠体内清除减慢。
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, authorsList=罗林, 黄冬, 张晓静, 李文斌, 王荣)}, authors=[Author(id=1236678242460037504, tenantId=1146029695717560320, journalId=1235980733773295621, articleId=1236678241235300669, orderNo=0, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=windguy@163.com, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1236678242594255242, tenantId=1146029695717560320, journalId=1235980733773295621, articleId=1236678241235300669, authorId=1236678242460037504, language=EN, stringName=Lin LUO, firstName=Lin, middleName=null, lastName=LUO, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=
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