title: Comparison of HT29-18-C1 and Caco-2 cell lines as models for studying intestinal paracellular drug absorption.
abstract: OBJECTIVE
  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 Omega x cm2). In contrast, Caco-2 monolayers rapidly develop Rt of approximately equal 300 Omega x cm2 and require Ca2+ -chelation to generate Rt equivalent to human intestine (60-120 Omega x cm2). Permeability of atenolol, ranitidine, cimetidine, hydrochlorothiazide and mannitol across HT29-18-C1 decreased 4-5 fold as Rt developed from 100-300 Omega x 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 Omega x 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.
authors.affiliation: Department of Medicine, University of Manchester, Hope Hospital, United Kingdom.
authors.forename: A
authors.initials: A
authors.lastname: Collett
authors.forename: E
authors.initials: E
authors.lastname: Sims
authors.forename: D
authors.initials: D
authors.lastname: Walker
authors.forename: Y L
authors.initials: YL
authors.lastname: He
authors.forename: J
authors.initials: J
authors.lastname: Ayrton
authors.forename: M
authors.initials: M
authors.lastname: Rowland
authors.forename: G
authors.initials: G
authors.lastname: Warhurst
mesh_terms: D001262:Atenolol / Q000493:pharmacokinetics; D001692:Biological Transport / Q000502:physiology; D018938:Caco-2 Cells / Q000166:cytology / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D002463:Cell Membrane Permeability / Q000502:physiology*; D002927:Cimetidine / Q000493:pharmacokinetics; D019073:HT29 Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D006852:Hydrochlorothiazide / Q000493:pharmacokinetics; D007408:Intestinal Absorption / Q000502:physiology*; D008353:Mannitol / Q000493:pharmacokinetics; D011899:Ranitidine / Q000493:pharmacokinetics; D014316:Tritium
chemical_list: D006852:Hydrochlorothiazide; D014316:Tritium; D008353:Mannitol; D001262:Atenolol; D002927:Cimetidine; D011899:Ranitidine