{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T03:20:59Z","timestamp":1761016859632},"reference-count":22,"publisher":"Wiley","issue":"5-6","license":[{"start":{"date-parts":[[2010,5,5]],"date-time":"2010-05-05T00:00:00Z","timestamp":1273017600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biopharm &amp; Drug Disp"],"published-print":{"date-parts":[[2010,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The present study explored the feasibility of a differential setup for the <jats:italic>in situ<\/jats:italic> perfusion technique with mesenteric cannulation in rats to assess drug interactions at the level of intestinal absorption. In contrast to the classic, parallel <jats:italic>in situ<\/jats:italic> perfusion setup, the differential approach aims to identify intestinal drug interactions in individual animals by exposing the perfused segment to a sequence of multiple conditions. First, the setup was validated by assessing the interaction between the P\u2010glycoprotein (P\u2010gp) inhibitor verapamil and the transport probes atenolol (paracellular transport), propranolol (transcellular) and talinolol (P\u2010gp mediated efflux). While transport of atenolol and propranolol remained constant for the total perfusion time (2\u2009h), a verapamil\u2010induced increase in talinolol transport was observed within individual rats (between 3.2\u2010 and 5.2\u2010fold). In comparison with the parallel setup, the differential <jats:italic>in situ<\/jats:italic> perfusion approach enhances the power to detect drug interactions with compounds that exhibit strong subject\u2010dependent permeability. This was demonstrated by identifying an interaction between amprenavir and ketoconazole (P\u2010gp and CYP3A inhibitor) in five out of seven rats (permeability increase between 1.9\u2010 and 4.2\u2010fold), despite high inter\u2010individual differences in intrinsic permeability for amprenavir. In combination with an increased throughput (up to 300%) and a reduced animal use (up to 50%), the enhanced power of the differential approach improves the utility of the biorelevant <jats:italic>in situ<\/jats:italic> perfusion technique with mesenteric blood sampling to elucidate the intestinal interaction profile of drugs and drug candidates. Copyright \u00a9 2010 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/bdd.710","type":"journal-article","created":{"date-parts":[[2010,5,5]],"date-time":"2010-05-05T12:15:14Z","timestamp":1273061714000},"page":"278-285","source":"Crossref","is-referenced-by-count":16,"title":["Validation of a differential <i>in situ<\/i> perfusion method with mesenteric blood sampling in rats for intestinal drug interaction profiling"],"prefix":"10.1002","volume":"31","author":[{"given":"Joachim","family":"Brouwers","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raf","family":"Mols","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pieter","family":"Annaert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Augustijns","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2010,6,25]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200241040-00001"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.2174\/1389200043489144"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1211\/jpp\/61.05.0002"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199936030-00004"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11095\u2010009\u20109924\u20100"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-74901-3_8"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.102.044719"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.109.026591"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1211\/jpp.57.12.0006"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.106.010801"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.2174\/138920007780655423"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.107.017483"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0928\u20100987(00)00195\u20100"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0169\u2010409X(01)00183\u20101"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/jps.20309"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2003.11.016"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11095\u2010007\u20109307\u20103"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2008.08.004"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0169\u2010409X(99)00027\u20107"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1018939006780"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/jps.20553"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2005.11.005"}],"container-title":["Biopharmaceutics &amp; Drug Disposition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbdd.710","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdd.710","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T11:55:46Z","timestamp":1693396546000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdd.710"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,6,25]]},"references-count":22,"journal-issue":{"issue":"5-6","published-print":{"date-parts":[[2010,7]]}},"alternative-id":["10.1002\/bdd.710"],"URL":"https:\/\/doi.org\/10.1002\/bdd.710","archive":["Portico"],"relation":{},"ISSN":["0142-2782","1099-081X"],"issn-type":[{"value":"0142-2782","type":"print"},{"value":"1099-081X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,6,25]]}}}