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

[Display omitted] 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...

Full description

Saved in:
Bibliographic Details
Published in:International journal of pharmaceutics 2017-07, Vol.527 (1-2), p.135-141
Main Authors: Lozoya-Agullo, Isabel, Zur, Moran, Fine-Shamir, Noa, Markovic, Milica, Cohen, Yael, Porat, Daniel, González-Álvarez, Isabel, González-Álvarez, Marta, Merino-Sanjuán, Matilde, Bermejo, Marival, Dahan, Arik
Format: Article
Language:English
Subjects:
Animals
Caco-2 Cells
colon
Colon - drug effects
Colon - metabolism
Humans
Intestinal Absorption
intestinal permeability
large intestine
Male
oral drug absorption
Perfusion - methods
perfusion study
Permeability
Pharmaceutical Preparations - metabolism
Rats
Rats, Wistar
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:[Display omitted] 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.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2017.05.018