Article(id=1322901699005906993, tenantId=1146029695717560320, journalId=1235980733773295621, issueId=1322901641049015115, 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=1620748800000, acceptedDateStr=2021-05-12, onlineDate=1793333943367, onlineDateStr=2026-10-30, pubDate=1626278400000, pubDateStr=2021-07-15, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793333943367, onlineIssueDateStr=2026-10-30, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793333943367, creator=13701087609, updateTime=1793333943367, updator=13701087609, issue=Issue{id=1322901641049015115, tenantId=1146029695717560320, journalId=1235980733773295621, year='2021', volume='30', issue='13', pageStart='1153', pageEnd='1248', issueExtLink='null', onlineDate='null', pubDate='1626278400000', pubDateStr='2021-07-15', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1793333929460, creator='13701087609', updateTime=1793333989426, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1322901892623376986, tenantId=1146029695717560320, journalId=1235980733773295621, issueId=1322901641049015115, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1322901892627571291, tenantId=1146029695717560320, journalId=1235980733773295621, issueId=1322901641049015115, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=1176, endPage=1183, ext={EN=ArticleExt(id=1322901699354034226, articleId=1322901699005906993, tenantId=1146029695717560320, journalId=1235980733773295621, language=EN, title=Intestinal permeability of conjugated estrogen using
in vivo and
in vitro models, columnId=null, journalTitle=Chinese Journal of New Drugs, columnName=null, runingTitle=null, highlight=null, articleAbstract=
Objective: Taking major components of conjugated estrogen (CE), sodium equilin sulfate (EqS) and sodium estrone sulfate (ES), as examples to investigate their absorption characteristics in the rat intestine, and to evaluate two intestinal models.
Methods: Determination method of EqS and ES using atenolol as an internal standard by HPLC was delevloped. Models of in situ single-pass intestinal perfusions (SPIP) and Ussing Chamber rat intestine were applied for this study. The samples of intestinal sac fluid and receiving fluid at different time points after dosages of EqS+ES and atenolol. The parameters of effective permeability (Peff) and apparent permeability (Papp) were calculated and compared with that of atenolol.
Results: The linearity of the HPLC analysis methods for the two intestinal models is well correlated within a certain concentration range (r>0.999), the intra-day and inter-day precisions are both below 15%, the accuracy is between 85%~115%, and the recovery is greater than 70%. In SPIP rat model, no statistical difference was found between the Peff of EqS+ES (jejunum: 0.22±0.07×10-4, cm·s-1; ileum: 0.24±0.08×10-4, cm·s-1) and atenolol (jejunum: 0.18±0.11×10-4, cm·s-1; ileum: 0.32±0.15×10-4, cm·s-1) in jejunum and ileum (P空=0.373; P回=0.128). In Ussing Chamber rat intestine model, EqS+ES and atenolol were absorbed in all intestinal segments of rats (duodenum: 1.83±0.77×10-6, cm·s-1, 5.46±0.80×10-6, cm·s-1; jejunum: 6.93±1.43×10-6, cm·s-1, 10.04±1.16×10-6, cm·s-1; ileum: 6.96±1.28×10-6, cm·s-1, 6.28±0.82×10-6; colon: 10.03±2.07×10-6, cm·s-1, 11.09±1.08×10-6, cm·s-1). There was no statistical difference between Papp of EqS+ES and atenolol in the ileum and colon (Pileum=0.251; Pcolon=0.263). Atenolol is a alkaline compound, the permeability of which in ileum was higher than that in Jejunum theoretically. The in vitro model differs from the theory.
Conclusion: CE can be considered as a drug with moderate permeability. SPIP rat model among the two models seems more accurate and reliable.
, authors=Xiao-hang LIU
1, Liang ZHANG
1, Xin-rong LI
3, Yu SHAN
1, Xiao-li GAO
1, 2, authorsList=Xiao-hang LIU, Liang ZHANG, Xin-rong LI, Yu SHAN, Xiao-li GAO, authorCompany=null, correspAuthors=Xiao-li GAO, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1322901699832184883, articleId=1322901699005906993, tenantId=1146029695717560320, journalId=1235980733773295621, language=CN, title=结合雌激素肠道渗透性的在体与离体2种模型研究, columnId=1236331161786569054, journalTitle=中国新药杂志, columnName=重大新药创制专项巡礼, runingTitle=null, highlight=null, articleAbstract=
目的： 以结合雌激素（conjugated estrogen，CE）中主要活性成分马烯雌酮硫酸钠（sodium equilin sulfate，EqS）和雌酮硫酸钠（sodium estrone sulfate，ES）为代表研究CE在大鼠肠道的吸收特性，并评价2种肠道模型。
方法： 建立EqS，ES与阿替洛尔的HPLC方法，采用大鼠在体单向肠灌流（SPIP）与Ussing Chamber小肠模型，将阿替洛尔视为内标一同给药后收集EqS+ES与阿替洛尔不同时间点肠囊液及接收液，计算有效渗透系数（Peff）和表观渗透系数（Papp）并与阿替洛尔比较。
结果： 2种肠道模型HPLC法的线性在一定浓度范围内相关性良好（r>0.999），日内、间精密度均小于15%，准确度在85%~115%，提取回收率均大于70%。大鼠SPIP模型中，EqS+ES的Peff [空肠：（0.22±0.07）×10-4 cm·s-1，回肠：（0.24±0.08）×10-4 cm·s-1）]与阿替洛尔[空肠：（0.18±0.11）×10-4 cm·s-1，回肠：（0.32±0.15）×10-4 cm·s-1）]在2个肠段无统计学差异（P空=0.373；P回=0.128）；Ussing Chamber大鼠小肠模型中，EqS+ES与阿替洛尔在4个肠段均有吸收[十二指肠：（1.83±0.77）×10-6 cm·s-1，（5.46±0.80）×10-6 cm·s-1；空肠：（6.93±1.43）×10-6 cm·s-1，（10.04±1.16）×10-6 cm·s-1；回肠：（6.96±1.28）×10-6 cm·s-1，（6.28±0.82）×10-6 cm·s-1；结肠：（10.03±2.07）×10-6 cm·s-1，（11.09±1.08）×10-6 cm·s-1）]，其中EqS+ES在回肠和结肠中的Papp与阿替洛尔比较无统计学差异（P回=0.251，P结=0.263）；阿替洛尔是碱性化合物，理论上回肠的渗透性应高于空肠，离体模型与理论有差异。
结论： CE可能为中等吸收药物，2种模型中大鼠SPIP模型似乎更加准确可靠。
, authors=刘晓航
1, 张亮
1, 李欣荣
3, 单宇
1, 高晓黎
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