Systematic studies on the paracellular permeation of model permeants and oligonucleotides in the rat small intestine with chenodeoxycholate as enhancer.
Identifieur interne : 002161 ( PubMed/Curation ); précédent : 002160; suivant : 002162Systematic studies on the paracellular permeation of model permeants and oligonucleotides in the rat small intestine with chenodeoxycholate as enhancer.
Auteurs : Keiko Tsutsumi [États-Unis] ; S Kevin Li ; Richard V. Hymas ; Ching-Leou Teng ; Lloyd G. Tillman ; Gregory E. Hardee ; William I. Higuchi ; Norman F H. HoSource :
- Journal of pharmaceutical sciences [ 0022-3549 ] ; 2008.
Descripteurs français
- KwdFr :
- Absorption intestinale (), Acides et sels biliaires (métabolisme), Algorithmes, Animaux, Biodisponibilité, Chimie physique, Chénodiol (pharmacocinétique), Chénodiol (pharmacologie), Excipients, Iléum (), Iléum (cytologie), Iléum (métabolisme), Indicateurs et réactifs, Intestin grêle (), Intestin grêle (cytologie), Intestin grêle (métabolisme), Jonctions serrées (), Jonctions serrées (ultrastructure), Jéjunum (), Jéjunum (cytologie), Jéjunum (métabolisme), Mannitol (pharmacocinétique), Mâle, Mésentère (métabolisme), Oligonucléotides (pharmacocinétique), Perfusion, Phénomènes chimiques, Porosité, Raffinose (pharmacocinétique), Rat Sprague-Dawley, Rats, Techniques in vitro, Urée (pharmacocinétique).
- MESH :
- cytologie : Iléum, Intestin grêle, Jéjunum.
- métabolisme : Acides et sels biliaires, Iléum, Intestin grêle, Jéjunum, Mésentère.
- pharmacocinétique : Chénodiol, Mannitol, Oligonucléotides, Raffinose, Urée.
- pharmacologie : Chénodiol.
- Absorption intestinale, Algorithmes, Animaux, Biodisponibilité, Chimie physique, Excipients, Iléum, Indicateurs et réactifs, Intestin grêle, Jonctions serrées, Jéjunum, Mâle, Perfusion, Phénomènes chimiques, Porosité, Rat Sprague-Dawley, Rats, Techniques in vitro.
English descriptors
- KwdEn :
- Algorithms, Animals, Bile Acids and Salts (metabolism), Biological Availability, Chemical Phenomena, Chemistry, Physical, Chenodeoxycholic Acid (pharmacokinetics), Chenodeoxycholic Acid (pharmacology), Excipients, Ileum (cytology), Ileum (drug effects), Ileum (metabolism), In Vitro Techniques, Indicators and Reagents, Intestinal Absorption (drug effects), Intestine, Small (cytology), Intestine, Small (drug effects), Intestine, Small (metabolism), Jejunum (cytology), Jejunum (drug effects), Jejunum (metabolism), Male, Mannitol (pharmacokinetics), Mesentery (metabolism), Oligonucleotides (pharmacokinetics), Perfusion, Porosity, Raffinose (pharmacokinetics), Rats, Rats, Sprague-Dawley, Tight Junctions (drug effects), Tight Junctions (ultrastructure), Urea (pharmacokinetics).
- MESH :
- chemical , metabolism : Bile Acids and Salts.
- chemical , pharmacokinetics : Chenodeoxycholic Acid, Mannitol, Oligonucleotides, Raffinose, Urea.
- chemical , pharmacology : Chenodeoxycholic Acid.
- cytology : Ileum, Intestine, Small, Jejunum.
- drug effects : Ileum, Intestinal Absorption, Intestine, Small, Jejunum, Tight Junctions.
- metabolism : Ileum, Intestine, Small, Jejunum, Mesentery.
- ultrastructure : Tight Junctions.
- Algorithms, Animals, Biological Availability, Chemical Phenomena, Chemistry, Physical, Excipients, In Vitro Techniques, Indicators and Reagents, Male, Perfusion, Porosity, Rats, Rats, Sprague-Dawley.
Abstract
The objective of this study was to mechanistically and quantitatively analyze chenodeoxycholate-enhanced paracellular transport of polar permeants and oligonucleotides in the rat jejunum and ileum. Micellar chenodeoxycholate solutions were used to perturbate the tight junctions. Supporting studies included assessment of the aqueous boundary layer (ABL) with ABL-controlled permeants, measurements of the permeability coefficients and fluxes of the bile acid in dilute and micellar concentrations, and determinations of pore sizes with paracellular probes (urea, mannitol, and raffinose). The paracellular permeability coefficients, P(para), of two model oligonucleotides (ON3 and ON6; 12- and 24-mers with 11 and 23 negative charges, respectively) were determined. The enhanced permeabilities paralleled the increased fluxes of micellar bile salt solutions into mesenteric blood and the opening of the tight junctions as compared to controls. As the pore radius increased from 0.7 nm to a maximum of 2.4 nm in the jejunum and ileum, the absorption of ON3 was enhanced up to sixfold in the jejunum and about 14-fold in the ileum with P(para) values between 0.5 x 10(-6) and 6 x 10(-6) cm/s, whereas ON6 was enhanced up to twofold in the jejunum and fivefold in the ileum with permeabilities between 0.3 x 10(-6) and 2 x 10(-6) cm/s.
DOI: 10.1002/jps.21093
PubMed: 17847071
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Hymas</name></author><author><name sortKey="Teng, Ching Leou" sort="Teng, Ching Leou" uniqKey="Teng C" first="Ching-Leou" last="Teng">Ching-Leou Teng</name></author><author><name sortKey="Tillman, Lloyd G" sort="Tillman, Lloyd G" uniqKey="Tillman L" first="Lloyd G" last="Tillman">Lloyd G. Tillman</name></author><author><name sortKey="Hardee, Gregory E" sort="Hardee, Gregory E" uniqKey="Hardee G" first="Gregory E" last="Hardee">Gregory E. Hardee</name></author><author><name sortKey="Higuchi, William I" sort="Higuchi, William I" uniqKey="Higuchi W" first="William I" last="Higuchi">William I. Higuchi</name></author><author><name sortKey="Ho, Norman F H" sort="Ho, Norman F H" uniqKey="Ho N" first="Norman F H" last="Ho">Norman F H. 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(drug effects)</term><term>Jejunum (metabolism)</term><term>Male</term><term>Mannitol (pharmacokinetics)</term><term>Mesentery (metabolism)</term><term>Oligonucleotides (pharmacokinetics)</term><term>Perfusion</term><term>Porosity</term><term>Raffinose (pharmacokinetics)</term><term>Rats</term><term>Rats, Sprague-Dawley</term><term>Tight Junctions (drug effects)</term><term>Tight Junctions (ultrastructure)</term><term>Urea (pharmacokinetics)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Absorption intestinale ()</term><term>Acides et sels biliaires (métabolisme)</term><term>Algorithmes</term><term>Animaux</term><term>Biodisponibilité</term><term>Chimie physique</term><term>Chénodiol (pharmacocinétique)</term><term>Chénodiol (pharmacologie)</term><term>Excipients</term><term>Iléum ()</term><term>Iléum (cytologie)</term><term>Iléum (métabolisme)</term><term>Indicateurs et réactifs</term><term>Intestin grêle ()</term><term>Intestin grêle (cytologie)</term><term>Intestin grêle (métabolisme)</term><term>Jonctions serrées ()</term><term>Jonctions serrées (ultrastructure)</term><term>Jéjunum ()</term><term>Jéjunum (cytologie)</term><term>Jéjunum (métabolisme)</term><term>Mannitol (pharmacocinétique)</term><term>Mâle</term><term>Mésentère (métabolisme)</term><term>Oligonucléotides (pharmacocinétique)</term><term>Perfusion</term><term>Phénomènes chimiques</term><term>Porosité</term><term>Raffinose (pharmacocinétique)</term><term>Rat Sprague-Dawley</term><term>Rats</term><term>Techniques in vitro</term><term>Urée (pharmacocinétique)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Bile Acids and Salts</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Chenodeoxycholic Acid</term><term>Mannitol</term><term>Oligonucleotides</term><term>Raffinose</term><term>Urea</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Chenodeoxycholic Acid</term></keywords><keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Iléum</term><term>Intestin grêle</term><term>Jéjunum</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Ileum</term><term>Intestine, Small</term><term>Jejunum</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Ileum</term><term>Intestinal Absorption</term><term>Intestine, Small</term><term>Jejunum</term><term>Tight Junctions</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Ileum</term><term>Intestine, Small</term><term>Jejunum</term><term>Mesentery</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Acides et sels biliaires</term><term>Iléum</term><term>Intestin grêle</term><term>Jéjunum</term><term>Mésentère</term></keywords><keywords scheme="MESH" qualifier="pharmacocinétique" xml:lang="fr"><term>Chénodiol</term><term>Mannitol</term><term>Oligonucléotides</term><term>Raffinose</term><term>Urée</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Chénodiol</term></keywords><keywords scheme="MESH" qualifier="ultrastructure" xml:lang="en"><term>Tight Junctions</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Algorithms</term><term>Animals</term><term>Biological Availability</term><term>Chemical Phenomena</term><term>Chemistry, Physical</term><term>Excipients</term><term>In Vitro Techniques</term><term>Indicators and Reagents</term><term>Male</term><term>Perfusion</term><term>Porosity</term><term>Rats</term><term>Rats, Sprague-Dawley</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Absorption intestinale</term><term>Algorithmes</term><term>Animaux</term><term>Biodisponibilité</term><term>Chimie physique</term><term>Excipients</term><term>Iléum</term><term>Indicateurs et réactifs</term><term>Intestin grêle</term><term>Jonctions serrées</term><term>Jéjunum</term><term>Mâle</term><term>Perfusion</term><term>Phénomènes chimiques</term><term>Porosité</term><term>Rat Sprague-Dawley</term><term>Rats</term><term>Techniques in vitro</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The objective of this study was to mechanistically and quantitatively analyze chenodeoxycholate-enhanced paracellular transport of polar permeants and oligonucleotides in the rat jejunum and ileum. Micellar chenodeoxycholate solutions were used to perturbate the tight junctions. Supporting studies included assessment of the aqueous boundary layer (ABL) with ABL-controlled permeants, measurements of the permeability coefficients and fluxes of the bile acid in dilute and micellar concentrations, and determinations of pore sizes with paracellular probes (urea, mannitol, and raffinose). The paracellular permeability coefficients, P(para), of two model oligonucleotides (ON3 and ON6; 12- and 24-mers with 11 and 23 negative charges, respectively) were determined. The enhanced permeabilities paralleled the increased fluxes of micellar bile salt solutions into mesenteric blood and the opening of the tight junctions as compared to controls. As the pore radius increased from 0.7 nm to a maximum of 2.4 nm in the jejunum and ileum, the absorption of ON3 was enhanced up to sixfold in the jejunum and about 14-fold in the ileum with P(para) values between 0.5 x 10(-6) and 6 x 10(-6) cm/s, whereas ON6 was enhanced up to twofold in the jejunum and fivefold in the ileum with permeabilities between 0.3 x 10(-6) and 2 x 10(-6) cm/s.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">17847071</PMID><DateCompleted><Year>2008</Year><Month>02</Month><Day>21</Day></DateCompleted><DateRevised><Year>2016</Year><Month>11</Month><Day>24</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0022-3549</ISSN><JournalIssue CitedMedium="Print"><Volume>97</Volume><Issue>1</Issue><PubDate><Year>2008</Year><Month>Jan</Month></PubDate></JournalIssue><Title>Journal of pharmaceutical sciences</Title><ISOAbbreviation>J Pharm Sci</ISOAbbreviation></Journal><ArticleTitle>Systematic studies on the paracellular permeation of model permeants and oligonucleotides in the rat small intestine with chenodeoxycholate as enhancer.</ArticleTitle><Pagination><MedlinePgn>350-67</MedlinePgn></Pagination><Abstract><AbstractText>The objective of this study was to mechanistically and quantitatively analyze chenodeoxycholate-enhanced paracellular transport of polar permeants and oligonucleotides in the rat jejunum and ileum. Micellar chenodeoxycholate solutions were used to perturbate the tight junctions. Supporting studies included assessment of the aqueous boundary layer (ABL) with ABL-controlled permeants, measurements of the permeability coefficients and fluxes of the bile acid in dilute and micellar concentrations, and determinations of pore sizes with paracellular probes (urea, mannitol, and raffinose). The paracellular permeability coefficients, P(para), of two model oligonucleotides (ON3 and ON6; 12- and 24-mers with 11 and 23 negative charges, respectively) were determined. The enhanced permeabilities paralleled the increased fluxes of micellar bile salt solutions into mesenteric blood and the opening of the tight junctions as compared to controls. As the pore radius increased from 0.7 nm to a maximum of 2.4 nm in the jejunum and ileum, the absorption of ON3 was enhanced up to sixfold in the jejunum and about 14-fold in the ileum with P(para) values between 0.5 x 10(-6) and 6 x 10(-6) cm/s, whereas ON6 was enhanced up to twofold in the jejunum and fivefold in the ileum with permeabilities between 0.3 x 10(-6) and 2 x 10(-6) cm/s.</AbstractText><CopyrightInformation>(c) 2007 Wiley-Liss, Inc.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Tsutsumi</LastName><ForeName>Keiko</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, 30 South 2000 East, Salt Lake City, UT 84112, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>S Kevin</ForeName><Initials>SK</Initials></Author><Author ValidYN="Y"><LastName>Hymas</LastName><ForeName>Richard V</ForeName><Initials>RV</Initials></Author><Author ValidYN="Y"><LastName>Teng</LastName><ForeName>Ching-Leou</ForeName><Initials>CL</Initials></Author><Author ValidYN="Y"><LastName>Tillman</LastName><ForeName>Lloyd G</ForeName><Initials>LG</Initials></Author><Author ValidYN="Y"><LastName>Hardee</LastName><ForeName>Gregory E</ForeName><Initials>GE</Initials></Author><Author ValidYN="Y"><LastName>Higuchi</LastName><ForeName>William I</ForeName><Initials>WI</Initials></Author><Author ValidYN="Y"><LastName>Ho</LastName><ForeName>Norman F H</ForeName><Initials>NF</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Pharm Sci</MedlineTA><NlmUniqueID>2985195R</NlmUniqueID><ISSNLinking>0022-3549</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D001647">Bile Acids and Salts</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D005079">Excipients</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007202">Indicators and Reagents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D009841">Oligonucleotides</NameOfSubstance></Chemical><Chemical><RegistryNumber>0GEI24LG0J</RegistryNumber><NameOfSubstance UI="D002635">Chenodeoxycholic Acid</NameOfSubstance></Chemical><Chemical><RegistryNumber>3OWL53L36A</RegistryNumber><NameOfSubstance UI="D008353">Mannitol</NameOfSubstance></Chemical><Chemical><RegistryNumber>8W8T17847W</RegistryNumber><NameOfSubstance UI="D014508">Urea</NameOfSubstance></Chemical><Chemical><RegistryNumber>N5O3QU595M</RegistryNumber><NameOfSubstance UI="D011887">Raffinose</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000465" MajorTopicYN="N">Algorithms</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001647" MajorTopicYN="N">Bile Acids and Salts</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001682" MajorTopicYN="N">Biological Availability</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D055598" MajorTopicYN="N">Chemical Phenomena</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002627" MajorTopicYN="N">Chemistry, Physical</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002635" MajorTopicYN="N">Chenodeoxycholic Acid</DescriptorName><QualifierName UI="Q000493" MajorTopicYN="Y">pharmacokinetics</QualifierName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005079" MajorTopicYN="N">Excipients</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007082" MajorTopicYN="N">Ileum</DescriptorName><QualifierName UI="Q000166" MajorTopicYN="N">cytology</QualifierName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D066298" MajorTopicYN="N">In Vitro Techniques</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007202" MajorTopicYN="N">Indicators and Reagents</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007408" MajorTopicYN="N">Intestinal Absorption</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007421" MajorTopicYN="N">Intestine, Small</DescriptorName><QualifierName UI="Q000166" MajorTopicYN="N">cytology</QualifierName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007583" MajorTopicYN="N">Jejunum</DescriptorName><QualifierName UI="Q000166" MajorTopicYN="N">cytology</QualifierName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008353" MajorTopicYN="N">Mannitol</DescriptorName><QualifierName UI="Q000493" MajorTopicYN="N">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008643" MajorTopicYN="N">Mesentery</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009841" MajorTopicYN="N">Oligonucleotides</DescriptorName><QualifierName UI="Q000493" MajorTopicYN="Y">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010477" MajorTopicYN="N">Perfusion</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016062" MajorTopicYN="N">Porosity</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011887" MajorTopicYN="N">Raffinose</DescriptorName><QualifierName UI="Q000493" MajorTopicYN="N">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051381" MajorTopicYN="N">Rats</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017207" MajorTopicYN="N">Rats, Sprague-Dawley</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019108" MajorTopicYN="N">Tight Junctions</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000648" MajorTopicYN="N">ultrastructure</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014508" MajorTopicYN="N">Urea</DescriptorName><QualifierName UI="Q000493" MajorTopicYN="N">pharmacokinetics</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2007</Year><Month>9</Month><Day>12</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2008</Year><Month>2</Month><Day>22</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2007</Year><Month>9</Month><Day>12</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">17847071</ArticleId><ArticleId IdType="doi">10.1002/jps.21093</ArticleId><ArticleId IdType="pii">S0022-3549(16)32469-8</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix 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