Investigating drug absorption from the colon: Single-pass vs. Doluisio approaches to in-situ rat large-intestinal perfusion

Isabel Lozoya-Agullo, Moran Zur, Noa Fine-Shamir, Milica Markovic, Yael Cohen, Daniel Porat, Isabel González-Álvarez, Marta González-Álvarez, Matilde Merino-Sanjuán, Marival Bermejo, Arik Dahan

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Traditionally, the colon is considered a secondary intestinal segment in the drug absorption process. However, in many cases the role of colonic drug permeability cannot be overlooked. The purpose of this research was to compare colon permeability data obtained using two different rat perfusion methods the single-pass intestinal perfusion (SPIP) approach and the closed-loop (Doluisio) perfusion model. A list of 14 structurally diverse model drugs was constructed, and their rat colon permeability was studied using the two methods. The two sets of results were compared to each other, and were evaluated vs. in-vitro, ex-vivo, and in-vivo literature values. The SPIP and the Doluisio results exhibited good correlation between them (R2 = 0.81). The best correlation of both sets was obtained with transport studies across Caco-2 monolayers (R2 ∼ 0.9), as well as the sigmoidal fit vs. human fraction of dose absorbed (Fabs) data. On the other hand, Ussing chambers data, as well as lipophilicity (Log P) data, resulted in weak correlation to the in-situ results. In conclusion, the single-pass intestinal perfusion (SPIP) and the Doluisio (closed-loop) perfusion models were found to be equally convenient and useful for obtaining validated colon permeability values, although more human colonic Fabs data are needed for a better understanding of colonic drug permeability and absorption.

Original languageEnglish
Pages (from-to)135-141
Number of pages7
JournalInternational Journal of Pharmaceutics
Volume527
Issue number1-2
DOIs
StatePublished - 15 Jul 2017

Keywords

  • colon
  • intestinal permeability
  • large intestine
  • oral drug absorption
  • perfusion study

ASJC Scopus subject areas

  • Pharmaceutical Science

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