{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T21:04:06Z","timestamp":1789592646163,"version":"build-2803163510"},"reference-count":18,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,8,13]],"date-time":"2018-08-13T00:00:00Z","timestamp":1534118400000},"content-version":"vor","delay-in-days":43,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Grants-in-Aid for Scientific Research KAKENHI","award":["25460196"],"award-info":[{"award-number":["25460196"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biopharm &amp; Drug Disp"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Indoxyl sulfate (IS) is a protein\u2010bound uremic toxin that progressively accumulates in plasma during chronic kidney disease (CKD), and its accumulation is associated with the progression of CKD. This study examined the intestinal secretion of IS using <jats:italic>in situ<\/jats:italic> single\u2010pass intestinal perfusion in a rat model of renal insufficiency, MRP2\u2010 and BCRP\u2010overexpressing Sf9 membrane vesicles, and Caco\u20102 cell monolayers. An <jats:italic>in situ<\/jats:italic> single\u2010pass perfusion study in CKD model rats demonstrated that a small amount of IS is secreted into intestinal lumen after iv administration of IS, and the clearance increased AUC\u2010dependently. An excess amount of IS (3\u00a0m<jats:sc>m<\/jats:sc>) partially inhibited the MRP2\u2010 and BCRP\u2010mediated uptake of specific fluorescent substrates, CDCF and Lucifer yellow, respectively, into the membrane vesicles, although IS was not taken up at a physiological concentration, 10 \u03bc<jats:sc>m<\/jats:sc>. In the Caco\u20102 cell monolayers, the IS transport was higher in the absorptive direction than in the secretory direction (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05). p\u2010Aminohippuric acid (PAH) strongly inhibited IS transport in both directions (absorptive, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.142; secretory, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.01). Given that the blood IS levels are much higher than those in the intestinal lumen, it is possible that this unknown PAH\u2010sensitive system contributes to the intestinal IS secretion. Although <jats:italic>in situ<\/jats:italic> inhibition study is needed to confirm that this unknown transporter mediates the <jats:italic>in vivo<\/jats:italic> intestinal secretion of IS, we speculate that this unknown active efflux system works as a compensatory excretion pathway for excess organic anions such as IS especially in end\u2010stage renal disease.<\/jats:p>","DOI":"10.1002\/bdd.2149","type":"journal-article","created":{"date-parts":[[2018,7,5]],"date-time":"2018-07-05T23:29:21Z","timestamp":1530833361000},"page":"328-334","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Intestinal secretion of indoxyl sulfate as a possible compensatory excretion pathway in chronic kidney disease"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5328-8843","authenticated-orcid":false,"given":"Kaori","family":"Morimoto","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy 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