Acamprosate has no impact on the permeability of paracellular markers across Caco-2 cells

Irina Antonescu, Bente Steffansen, Sibylle Neuhoff

Research output: Contribution to conference without publisher/journalPosterResearchpeer-review

Abstract

Backgrounds: The oral bioavailability of poorly permeable and non-metabolised acamprosate (BCS III) is 11%. It is controversial whether the intestinal effective permeability of the fully an-ionized acamprosate (pKa 1.83; MW 181.2 g/mol) is predominantly paracellular (Ppara) or transcellular. An initial physiologically-based pharmacokinetic model indicates that Ppara can’t account for acamprosate absorption and suggests involvement of carrier-mediated transport. However, an alternative explanation could be that acamprosate enhances its own Ppara. Aims: The effect of acamprosate on Ppara of the paracellular markers, mannitol and Lucifer Yellow (LY), was investigated.
Methods: Ppara of LY and [14C]-mannitol was investigated across filter grown human epithelial colorectal adenocarcinoma (Caco-2) cell monolayers. Changes in the transepithelial electrical resistance (TEER) across the monolayers were evaluated. Results: LY and [14C]-mannitol Ppara values were not significantly different in presence 0.43±0.06x10-6 and 0.47±0.24x10-6 cm/s or absence 0.30±0.08x10-6 and 0.43±0.20x10-6 cm/s (Mean±SD, n=3) of acamprosate, respectively. Pre-treated cells with acamprosate for 24 or 4 hours before applying the [14C]-mannitol, Papp values of 0.71±0.2x10-6 and 0.51±0.17x10-6 cm/s were obtained. TEER values at the end of all experiments were in the range of 426-444 ohm*cm2. Summary/Conclusion: Acamprosate has no impact on the paracellular pathway across Caco-2 cell monolayers of LY and mannitol, or on the TEER values. This consolidates the hypothesis that intestinal transporters might play a role in the absorption of acamprosate.
Original languageEnglish
Publication date22. May 2017
Number of pages1
Publication statusPublished - 22. May 2017
Event6th FIP Pharmaceutical Sciences World Congress 2017: Future Medicines For One World - Systems approaches to drug discovery, development and clinical usage - Stockholmsmässan, Stockholm, Sweden
Duration: 21. May 201724. May 2017
http://pswc2017.fip.org/home

Conference

Conference6th FIP Pharmaceutical Sciences World Congress 2017
LocationStockholmsmässan
CountrySweden
CityStockholm
Period21/05/201724/05/2017
Internet address

Keywords

  • paracellular pathway
  • Caco-2 Cells
  • drug absorption
  • Intestinal Absorption
  • paracellular integrity markers
  • TEER

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