TY - JOUR
T1 - Investigating drug absorption from the colon
T2 - Single-pass vs. Doluisio approaches to in-situ rat large-intestinal perfusion
AU - Lozoya-Agullo, Isabel
AU - Zur, Moran
AU - Fine-Shamir, Noa
AU - Markovic, Milica
AU - Cohen, Yael
AU - Porat, Daniel
AU - González-Álvarez, Isabel
AU - González-Álvarez, Marta
AU - Merino-Sanjuán, Matilde
AU - Bermejo, Marival
AU - Dahan, Arik
N1 - Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2017/7/15
Y1 - 2017/7/15
N2 - 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.
AB - 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.
KW - colon
KW - intestinal permeability
KW - large intestine
KW - oral drug absorption
KW - perfusion study
UR - http://www.scopus.com/inward/record.url?scp=85019765680&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2017.05.018
DO - 10.1016/j.ijpharm.2017.05.018
M3 - Article
AN - SCOPUS:85019765680
SN - 0378-5173
VL - 527
SP - 135
EP - 141
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1-2
ER -