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Comparison of HT29-18-C1 and Caco-2 cell lines as models for studying intestinal paracellular drug absorption

Comparison of HT29-18-C1 and Caco-2 cell lines as models for studying intestinal paracellular drug absorption
Comparison of HT29-18-C1 and Caco-2 cell lines as models for studying intestinal paracellular drug absorption
Purpose. To compare the permeability characteristics of HT29-18-C1 colonic epithelial cell line with Caco-2, an established model of intestinal drug transport.

Methods. Cell lines were grown as epithelial monolayers. Permeability was measured over a range of transepithelial electrical resistance (Rt) using a group of drug compounds.

Results. HT29-18-C1 develop Rt slowly when grown in culture, allowing permeability to be measured over a wide range (80–600 ?·cm2). In contrast, Caco-2 monolayers rapidly develop Rt of ?300 ?·cm2 and require Ca2+-chelation to generate Rt equivalent to human intestine (60–120 ?·cm2). Permeability of atenolol, ranitidine, cimetidine, hydrochlorothiazide and mannitol across HT29-18-C1 decreased 4–5 fold as Rt developed from 100–300 ?·cm2 indicating they permeate via the paracellular route. In contrast, ondansetron showed no difference in permeability with changing Rt consistent with transcellular permeation. Permeability profiles across low Rt HT29-18C1 and pulse EGTA-treated Caco-2 monolayers were the same for all 5 paracellular drugs suggesting that transient Ca2+ removal does not alter selectivity of the tight junctions. Permeabilities of cimetidine, hydrochlorothiazide and atenolol across 100 ?·cm2 HT29-18-C1 monolayers reflect more closely those reported for the human ileum in vivo than did mature Caco-2 monolayers.

Conclusions. HT29-18-C1 monolayers can be used to study drug permeability at Rt values similar to human intestine without the need for Ca2+ chelation. As such, they offer a useful alternative to Caco-2 for modelling intestinal drug absorption.
caco-2, HT29-18C1 cell lines, paracellular drug absorption
0724-8741
216-221
Collett, Andrew
ad03f98a-46a3-41a1-b979-fa47a0fd45cc
Sims, Erika
edb096ba-5eb7-4d1e-8973-82ec54de56e9
Walker, David
b94e6f46-ec02-4b5b-a726-67c0aafc9f94
He, Yan‐Ling
885a7e1a-8e77-4bee-8628-ddc4aa470197
Ayrton, John
1d0921cc-3d7c-4b4e-aea3-4b3129f97d56
Rowland, Malcolm
680cad77-67d7-4b71-a794-c745e64def7c
Warhurst, Geoffrey
74a5cea0-c1b9-4086-a780-0b4c5595ad0e
Collett, Andrew
ad03f98a-46a3-41a1-b979-fa47a0fd45cc
Sims, Erika
edb096ba-5eb7-4d1e-8973-82ec54de56e9
Walker, David
b94e6f46-ec02-4b5b-a726-67c0aafc9f94
He, Yan‐Ling
885a7e1a-8e77-4bee-8628-ddc4aa470197
Ayrton, John
1d0921cc-3d7c-4b4e-aea3-4b3129f97d56
Rowland, Malcolm
680cad77-67d7-4b71-a794-c745e64def7c
Warhurst, Geoffrey
74a5cea0-c1b9-4086-a780-0b4c5595ad0e

Collett, Andrew, Sims, Erika, Walker, David, He, Yan‐Ling, Ayrton, John, Rowland, Malcolm and Warhurst, Geoffrey (1996) Comparison of HT29-18-C1 and Caco-2 cell lines as models for studying intestinal paracellular drug absorption. Pharmaceutical Research, 13 (2), 216-221. (doi:10.1023/A:1016082829111). (PMID:8932439)

Record type: Article

Abstract

Purpose. To compare the permeability characteristics of HT29-18-C1 colonic epithelial cell line with Caco-2, an established model of intestinal drug transport.

Methods. Cell lines were grown as epithelial monolayers. Permeability was measured over a range of transepithelial electrical resistance (Rt) using a group of drug compounds.

Results. HT29-18-C1 develop Rt slowly when grown in culture, allowing permeability to be measured over a wide range (80–600 ?·cm2). In contrast, Caco-2 monolayers rapidly develop Rt of ?300 ?·cm2 and require Ca2+-chelation to generate Rt equivalent to human intestine (60–120 ?·cm2). Permeability of atenolol, ranitidine, cimetidine, hydrochlorothiazide and mannitol across HT29-18-C1 decreased 4–5 fold as Rt developed from 100–300 ?·cm2 indicating they permeate via the paracellular route. In contrast, ondansetron showed no difference in permeability with changing Rt consistent with transcellular permeation. Permeability profiles across low Rt HT29-18C1 and pulse EGTA-treated Caco-2 monolayers were the same for all 5 paracellular drugs suggesting that transient Ca2+ removal does not alter selectivity of the tight junctions. Permeabilities of cimetidine, hydrochlorothiazide and atenolol across 100 ?·cm2 HT29-18-C1 monolayers reflect more closely those reported for the human ileum in vivo than did mature Caco-2 monolayers.

Conclusions. HT29-18-C1 monolayers can be used to study drug permeability at Rt values similar to human intestine without the need for Ca2+ chelation. As such, they offer a useful alternative to Caco-2 for modelling intestinal drug absorption.

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More information

Published date: February 1996
Keywords: caco-2, HT29-18C1 cell lines, paracellular drug absorption
Organisations: Medical Education

Identifiers

Local EPrints ID: 359215
URI: https://eprints.soton.ac.uk/id/eprint/359215
ISSN: 0724-8741
PURE UUID: 9b7d59c8-9b6f-48e0-a7f4-78755e966fbf

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Date deposited: 23 Oct 2013 12:53
Last modified: 18 Jul 2017 03:22

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Contributors

Author: Andrew Collett
Author: Erika Sims
Author: David Walker
Author: Yan‐Ling He
Author: John Ayrton
Author: Malcolm Rowland
Author: Geoffrey Warhurst

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