Intraluminal Behavior of Various Transporter Substrates in the Rat Gastrointestinal Tract

Purpose: The aim of this study was to evaluate the intraluminal behavior of various transporter substrates in different regions of the gastrointestinal (GI) tract. Methods: Drug solutions containing non-absorbable FITC-dextran 4000 (FD-4), were orally administered to rats. Residual water was sample...

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Autores principales:	Yusuke Tanaka, Taiki Harada, Kazuhiro Ito, Takanori Kurakazu, Satoshi Kasaoka
Formato:	article
Lenguaje:	EN
Publicado:	Canadian Society for Pharmaceutical Sciences 2021
Materias:	Therapeutics. Pharmacology RM1-950 Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/15a4c67c5ec84d24bbc2bf8772379dbf
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spelling	oai:doaj.org-article:15a4c67c5ec84d24bbc2bf8772379dbf2021-12-02T18:38:02ZIntraluminal Behavior of Various Transporter Substrates in the Rat Gastrointestinal Tract10.18433/jpps323141482-1826https://doaj.org/article/15a4c67c5ec84d24bbc2bf8772379dbf2021-11-01T00:00:00Zhttps://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/32314https://doaj.org/toc/1482-1826 Purpose: The aim of this study was to evaluate the intraluminal behavior of various transporter substrates in different regions of the gastrointestinal (GI) tract. Methods: Drug solutions containing non-absorbable FITC-dextran 4000 (FD-4), were orally administered to rats. Residual water was sampled from the GI regions to measure the luminal drug concentration. Results: Cephalexin (CEX), a substrate of the proton-coupled oligopeptide transporter, was absorbed rapidly, and no drug was detected in the lower small intestine. Saquinavir (SQV) was primarily absorbed in the upper region. However, unlike CEX, SQV was detected even in the lower segment probably due to the efflux of SQV via P-glycoprotein (P-gp). The concentration of methotrexate (MTX) showed a similar pattern to that of non-absorbable FD-4. The low absorption of MTX was probably due to efflux via several efflux transporters, and the limited expression of proton-coupled folate transporter, an absorptive transporter for MTX, in the upper region. Conclusion: This study revealed that the luminal concentration pattern of each drug differed considerably depending on the site because of the different absorption properties and luminal volumes. Although further investigation using a specific transporter inhibitor or transporter-knockout animals are necessary to clarify the actual contribution of each transporter to the drug absorption, this information will be valuable in evaluating transporter-mediated drug absorption in in vitro transport studies for ensuring optimal drug concentrations. Yusuke TanakaTaiki HaradaKazuhiro ItoTakanori KurakazuSatoshi KasaokaCanadian Society for Pharmaceutical SciencesarticleTherapeutics. PharmacologyRM1-950Pharmacy and materia medicaRS1-441ENJournal of Pharmacy & Pharmaceutical Sciences, Vol 24 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Therapeutics. Pharmacology RM1-950 Pharmacy and materia medica RS1-441
spellingShingle	Therapeutics. Pharmacology RM1-950 Pharmacy and materia medica RS1-441 Yusuke Tanaka Taiki Harada Kazuhiro Ito Takanori Kurakazu Satoshi Kasaoka Intraluminal Behavior of Various Transporter Substrates in the Rat Gastrointestinal Tract
description	Purpose: The aim of this study was to evaluate the intraluminal behavior of various transporter substrates in different regions of the gastrointestinal (GI) tract. Methods: Drug solutions containing non-absorbable FITC-dextran 4000 (FD-4), were orally administered to rats. Residual water was sampled from the GI regions to measure the luminal drug concentration. Results: Cephalexin (CEX), a substrate of the proton-coupled oligopeptide transporter, was absorbed rapidly, and no drug was detected in the lower small intestine. Saquinavir (SQV) was primarily absorbed in the upper region. However, unlike CEX, SQV was detected even in the lower segment probably due to the efflux of SQV via P-glycoprotein (P-gp). The concentration of methotrexate (MTX) showed a similar pattern to that of non-absorbable FD-4. The low absorption of MTX was probably due to efflux via several efflux transporters, and the limited expression of proton-coupled folate transporter, an absorptive transporter for MTX, in the upper region. Conclusion: This study revealed that the luminal concentration pattern of each drug differed considerably depending on the site because of the different absorption properties and luminal volumes. Although further investigation using a specific transporter inhibitor or transporter-knockout animals are necessary to clarify the actual contribution of each transporter to the drug absorption, this information will be valuable in evaluating transporter-mediated drug absorption in in vitro transport studies for ensuring optimal drug concentrations.
format	article
author	Yusuke Tanaka Taiki Harada Kazuhiro Ito Takanori Kurakazu Satoshi Kasaoka
author_facet	Yusuke Tanaka Taiki Harada Kazuhiro Ito Takanori Kurakazu Satoshi Kasaoka
author_sort	Yusuke Tanaka
title	Intraluminal Behavior of Various Transporter Substrates in the Rat Gastrointestinal Tract
title_short	Intraluminal Behavior of Various Transporter Substrates in the Rat Gastrointestinal Tract
title_full	Intraluminal Behavior of Various Transporter Substrates in the Rat Gastrointestinal Tract
title_fullStr	Intraluminal Behavior of Various Transporter Substrates in the Rat Gastrointestinal Tract
title_full_unstemmed	Intraluminal Behavior of Various Transporter Substrates in the Rat Gastrointestinal Tract
title_sort	intraluminal behavior of various transporter substrates in the rat gastrointestinal tract
publisher	Canadian Society for Pharmaceutical Sciences
publishDate	2021
url	https://doaj.org/article/15a4c67c5ec84d24bbc2bf8772379dbf
work_keys_str_mv	AT yusuketanaka intraluminalbehaviorofvarioustransportersubstratesintheratgastrointestinaltract AT taikiharada intraluminalbehaviorofvarioustransportersubstratesintheratgastrointestinaltract AT kazuhiroito intraluminalbehaviorofvarioustransportersubstratesintheratgastrointestinaltract AT takanorikurakazu intraluminalbehaviorofvarioustransportersubstratesintheratgastrointestinaltract AT satoshikasaoka intraluminalbehaviorofvarioustransportersubstratesintheratgastrointestinaltract
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Intraluminal Behavior of Various Transporter Substrates in the Rat Gastrointestinal Tract

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