{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T13:53:38Z","timestamp":1791467618101,"version":"4.3.4"},"reference-count":27,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp;amp; Syst Pharma"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>A high number of poorly soluble compounds are being developed; thus, understanding the factors that influence their absorption is critical. Intestinal bile salts, which facilitate micelle\u2010mediated solubilization, are particularly important for drugs with low solubility and are reported to be highly variable. The aim of this study was to evaluate the effect of luminal bile salt concentrations on the absorption of poorly soluble compounds, using efavirenz, cinnarizine, and posaconazole as examples. Physiologically\u2010based pharmacokinetic (PBPK) models were developed and validated using the Simcyp Simulator. Sensitivity analyzes were performed to assess the impact of bile salts and other gastrointestinal parameters on drug absorption. Simulations revealed that drug absorption in the fasted state was most sensitive to bile salt concentrations compared to other gastrointestinal parameters such as luminal pH, fluid volumes, and gastric emptying. The findings indicate that efavirenz, cinnarizine, and posaconazole exhibit high micelle\u2010mediated solubility, with bile salts playing a critical role in their absorption, particularly in the fasted state. These results highlight the importance of considering bile salt concentrations in PBPK modeling of poorly soluble compounds.<\/jats:p>","DOI":"10.1002\/psp4.70177","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T11:41:13Z","timestamp":1768909273000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Evaluating the Impact of Intestinal Bile Salts on Drug Absorption Using PBPK Modeling: Case Studies With Efavirenz, Cinnarizine, and Posaconazole"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8010-9278","authenticated-orcid":false,"given":"Laura G.","family":"Al\u2010Amiry Santos","sequence":"first","affiliation":[{"name":"Certara UK Limited  Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8614-0642","authenticated-orcid":false,"given":"Sebastian","family":"Polak","sequence":"additional","affiliation":[{"name":"Certara UK Limited  Sheffield UK"},{"name":"Faculty of Pharmacy Jagiellonian University Medical College  Krakow Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7020-1970","authenticated-orcid":false,"given":"Karen Rowland","family":"Yeo","sequence":"additional","affiliation":[{"name":"Certara UK Limited  Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.618411"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2024.114513"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2018.07.037"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(80)90244-9"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(71)80053-7"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-025-01016-x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2016.04.018"},{"key":"e_1_2_9_9_1","unstructured":"U.S. Food and Drug Administration Efavirenz Biopharmaceutics Review(NDA 21\u2013360) (2002)."},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2016.01.011"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.2003.01977.x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-020-04179-w"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-009-9099-y"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdd.2072"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkab298"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12249-013-0016-4"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26227052"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-016-0038-4"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-013-1145-x"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI108156"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.109.031393"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2010.11.082"},{"key":"e_1_2_9_23_1","first-page":"407","article-title":"High\u2010Performance Liquid Chromatographic Assay for Cinnarizine in Human Plasma","volume":"64","author":"Nowacka\u2010Krukowska H.","year":"2007","journal-title":"Acta Poloniae Pharmaceutica"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3109\/10717544.2015.1064187"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(79)90154-9"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(79)90155-0"},{"key":"e_1_2_9_27_1","first-page":"437","article-title":"Clinical Exploration and Physiologically Based Modelling of the Impact of Hepatic Impairment on Entrectinib Pharmacokinetics","volume":"64","author":"Ozbey A. 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