Systematic studies on the paracellular permeation of model permeants and oligonucleotides in the rat small intestine with chenodeoxycholate as enhancer.
Identifieur interne : 000548 ( Ncbi/Checkpoint ); précédent : 000547; suivant : 000549Systematic 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
Affiliations:
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pubmed:17847071Le document en format XML
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<series><title level="j">Journal of pharmaceutical sciences</title>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Algorithms</term>
<term>Animals</term>
<term>Bile Acids and Salts (metabolism)</term>
<term>Biological Availability</term>
<term>Chemical Phenomena</term>
<term>Chemistry, Physical</term>
<term>Chenodeoxycholic Acid (pharmacokinetics)</term>
<term>Chenodeoxycholic Acid (pharmacology)</term>
<term>Excipients</term>
<term>Ileum (cytology)</term>
<term>Ileum (drug effects)</term>
<term>Ileum (metabolism)</term>
<term>In Vitro Techniques</term>
<term>Indicators and Reagents</term>
<term>Intestinal Absorption (drug effects)</term>
<term>Intestine, Small (cytology)</term>
<term>Intestine, Small (drug effects)</term>
<term>Intestine, Small (metabolism)</term>
<term>Jejunum (cytology)</term>
<term>Jejunum (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>
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<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>
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<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Chenodeoxycholic Acid</term>
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<term>Intestin grêle</term>
<term>Jéjunum</term>
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<keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Ileum</term>
<term>Intestine, Small</term>
<term>Jejunum</term>
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<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>
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<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Ileum</term>
<term>Intestine, Small</term>
<term>Jejunum</term>
<term>Mesentery</term>
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<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>
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<keywords scheme="MESH" qualifier="pharmacocinétique" xml:lang="fr"><term>Chénodiol</term>
<term>Mannitol</term>
<term>Oligonucléotides</term>
<term>Raffinose</term>
<term>Urée</term>
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<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Chénodiol</term>
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<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>
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<term>Perfusion</term>
<term>Porosity</term>
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<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>
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<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>
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<tree><noCountry><name sortKey="Hardee, Gregory E" sort="Hardee, Gregory E" uniqKey="Hardee G" first="Gregory E" last="Hardee">Gregory E. Hardee</name>
<name sortKey="Higuchi, William I" sort="Higuchi, William I" uniqKey="Higuchi W" first="William I" last="Higuchi">William I. Higuchi</name>
<name sortKey="Ho, Norman F H" sort="Ho, Norman F H" uniqKey="Ho N" first="Norman F H" last="Ho">Norman F H. Ho</name>
<name sortKey="Hymas, Richard V" sort="Hymas, Richard V" uniqKey="Hymas R" first="Richard V" last="Hymas">Richard V. Hymas</name>
<name sortKey="Li, S Kevin" sort="Li, S Kevin" uniqKey="Li S" first="S Kevin" last="Li">S Kevin Li</name>
<name sortKey="Teng, Ching Leou" sort="Teng, Ching Leou" uniqKey="Teng C" first="Ching-Leou" last="Teng">Ching-Leou Teng</name>
<name sortKey="Tillman, Lloyd G" sort="Tillman, Lloyd G" uniqKey="Tillman L" first="Lloyd G" last="Tillman">Lloyd G. Tillman</name>
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<country name="États-Unis"><region name="Utah"><name sortKey="Tsutsumi, Keiko" sort="Tsutsumi, Keiko" uniqKey="Tsutsumi K" first="Keiko" last="Tsutsumi">Keiko Tsutsumi</name>
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