{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T04:25:46Z","timestamp":1787199946441,"version":"build-2736575974"},"reference-count":35,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"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; Syst Pharma"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Physiologically based pharmacokinetic (PBPK) and physiologically\u2010based biopharmaceutics (PBBM) modeling are valuable tools in drug development, allowing mechanistic predictions of drug absorption and disposition. However, sex\u2010related differences in gastrointestinal physiology are often underrepresented in virtual populations, potentially limiting prediction accuracy. This study aimed to evaluate how sex\u2010related physiological differences are incorporated into commonly used PBPK platforms and to illustrate their impact on pharmacokinetic predictions using ketoprofen as a case study. Three PBPK platforms were systematically reviewed to assess predefined sex\u2010specific gastrointestinal parameters. All three platforms incorporated sex\u2010related differences in general anatomy and physiology but overlooked sex\u2010specific variability in gastrointestinal tract parameters. In addition, three PBBM models of ketoprofen were developed and verified in males and subsequently extrapolated to females using default and refined sex\u2010specific parameters. Under default female settings, the models overpredicted Cmax and underestimated Tmax, resulting in concentration\u2013time profiles that were nearly indistinguishable from those of males. Refining gastrointestinal tract parameters for females population improved prediction performance and better reflected observed sex differences. These findings indicate that current PBPK platforms may require user\u2010defined adjustments to adequately represent sex\u2010specific gastrointestinal physiology and that incorporating such parameters could lead to more representative PBBM applications.<\/jats:p>","DOI":"10.1002\/psp4.70310","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T04:18:54Z","timestamp":1785385134000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sex\u2010Related Differences in Physiologically\u2010Based Biopharmaceutics Modeling"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0507-6982","authenticated-orcid":false,"given":"Marianela","family":"Chavarr\u00eda\u2010Rojas","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Chemistry Universidad de la Rep\u00fablica  Montevideo Uruguay"},{"name":"Graduate Program in Chemistry, Faculty of Chemistry Universidad de la Rep\u00fablica  Montevideo Uruguay"},{"name":"Department of Industrial Pharmacy, Faculty of Pharmacy Universidad de Costa Rica  San Jos\u00e9 Costa Rica"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mubtasim","family":"Murshed","sequence":"additional","affiliation":[{"name":"University of Bath  Bath UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8330-6299","authenticated-orcid":false,"given":"Marianela","family":"Lorier","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Chemistry Universidad de la Rep\u00fablica  Montevideo Uruguay"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1826-7363","authenticated-orcid":false,"given":"Nikoletta","family":"Fotaki","sequence":"additional","affiliation":[{"name":"University of Bath  Bath UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0484-6367","authenticated-orcid":false,"given":"Manuel","family":"Ibarra","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Faculty of Chemistry Universidad de la Rep\u00fablica  Montevideo Uruguay"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3636"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2023.123267"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jddst.2022.103152"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2018.05.024"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.4c00202"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.05.014"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-019-01201-3"},{"issue":"46","key":"e_1_2_10_9_1","first-page":"61","article-title":"How to Study the Impact of Sex and Gender in Medical Research: A Review of Resources","volume":"7","author":"McGregor A. 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