{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T09:16:54Z","timestamp":1781428614476,"version":"3.54.1"},"reference-count":18,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,8,23]],"date-time":"2025-08-23T00:00:00Z","timestamp":1755907200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004328","name":"Genentech","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004328","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["2126329"],"award-info":[{"award-number":["2126329"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:p>Sulfasalazine, a cornerstone therapy for inflammatory bowel disease, relies on bacterial azo\u2010reduction to release its active component, 5\u2010aminosalicylic acid (5\u2010ASA), which is further metabolized into inactive N\u2010acetyl\u20105\u2010aminosalicylic acid (N\u2010acetyl\u20105\u2010ASA) by bacterial N\u2010acetyltransferase. Due to complex pharmacokinetics, patient\u2010specific microbial metabolism, and the lack of accurate, convenient direct sampling method for gastrointestinal drug concentrations, sulfasalazine clinical efficacy remains variable. The CapScan\u00ae luminal sampling device enables region\u2010specific, minimally invasive collection of intestinal contents. To better understand sulfasalazine pharmacokinetics in relation to intestinal and systemic drug concentrations and bacterial metabolic capacity, 10 healthy volunteers ingested CapScan devices following sulfasalazine administration. Upon retrieval from the stool, CapScan samples were assigned intestinal locations based on metabolomic and metagenomic profiling. Systemic sulfasalazine peaked at 4\u2009hours post\u2010ingestion, while 5\u2010ASA and N\u2010acetyl\u20105\u2010ASA peaked at 8\u2009hours. In the gastrointestinal tract, maximal sulfasalazine concentration was observed in the proximal small intestine (SI), decreasing distally as 5\u2010ASA and N\u2010acetyl\u20105\u2010ASA concentrations increased, peaking in the stool. 5\u2010ASA plasma concentrations positively correlated with distal SI concentrations 4\u2009hours after sulfasalazine ingestion. Putative bacterial azoreductase genes were detected in all gastrointestinal regions, while putative bacterial acetyltransferase genes were detected in all regions except the proximal SI. This study revealed spatially distinct luminal concentrations of sulfasalazine and its metabolites, with a strong correlation between distal SI 5\u2010ASA levels and early plasma exposure, highlighting GI region\u2010specific absorption and microbial metabolism. These findings support the potential utility of luminal sampling to enhance understanding of drug pharmacokinetics and inform future strategies for optimizing oral drug delivery.<\/jats:p>","DOI":"10.1002\/cpt.70035","type":"journal-article","created":{"date-parts":[[2025,8,23]],"date-time":"2025-08-23T18:00:26Z","timestamp":1755972026000},"page":"1437-1442","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Spatiotemporal Characterization of Sulfasalazine and 5\u2010\n                    <scp>ASA<\/scp>\n                    Pharmacokinetics Using a Noninvasive Intestinal Sampling Device"],"prefix":"10.1002","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3626-3350","authenticated-orcid":false,"given":"Jingwei","family":"Cai","sequence":"first","affiliation":[{"name":"Genentech Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan S.","family":"Mar","sequence":"additional","affiliation":[{"name":"Genentech Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bennett","family":"Kapili","sequence":"additional","affiliation":[{"name":"Envivo Bio Inc.  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly M.","family":"Storek","sequence":"additional","affiliation":[{"name":"Genentech Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmina","family":"Uzunovic","sequence":"additional","affiliation":[{"name":"Genentech Inc.  South San Francisco California USA"},{"name":"F. Hoffmann\u2010La Roche Ltd.  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Skippington","sequence":"additional","affiliation":[{"name":"Genentech Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Keilberg","sequence":"additional","affiliation":[{"name":"Genentech Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dewakar","family":"Sangaraju","sequence":"additional","affiliation":[{"name":"Genentech Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9638-7630","authenticated-orcid":false,"given":"Alexis","family":"Auster","sequence":"additional","affiliation":[{"name":"Genentech Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8385-9288","authenticated-orcid":false,"given":"Cyrus","family":"Khojasteh","sequence":"additional","affiliation":[{"name":"Genentech Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Horace","family":"Rhee","sequence":"additional","affiliation":[{"name":"Genentech Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4233-3773","authenticated-orcid":false,"given":"George","family":"Triadafilopoulos","sequence":"additional","affiliation":[{"name":"MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2646-6215","authenticated-orcid":false,"given":"Dari","family":"Shalon","sequence":"additional","affiliation":[{"name":"Envivo Bio Inc.  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Keir","sequence":"additional","affiliation":[{"name":"Genentech Inc.  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,23]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02217-7"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-05989-7"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio-2018-0241"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.5348"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/jasms.0c00435"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjae084"},{"key":"e_1_2_10_7_1","volume-title":"R: A Language and Environment for Statistical Computing","author":"Team, R. C","year":"2020"},{"key":"e_1_2_10_8_1","volume-title":"Sulfasalazine","author":"Choi J.","year":"2025"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.65088"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-198510040-00001"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2008.03751.x"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1988.tb03301.x"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.48.4.571"},{"key":"e_1_2_10_14_1","article-title":"Bioavailability enhancement techniques for poorly aqueous soluble drugs and therapeutics","volume":"10","author":"Bhalani D.V.","year":"2022","journal-title":"Biomedicine"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22020500"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2010.03.015"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph15121585"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.122.000898"}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/am-pdf\/10.1002\/cpt.70035","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.70035","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T04:38:26Z","timestamp":1763959106000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.70035"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,23]]},"references-count":18,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/cpt.70035"],"URL":"https:\/\/doi.org\/10.1002\/cpt.70035","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,23]]},"assertion":[{"value":"2025-05-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}