{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T09:48:22Z","timestamp":1782985702815,"version":"3.54.5"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-079149"],"award-info":[{"award-number":["INV-079149"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The female reproductive tract (FRT) is underrepresented in Physiologically-Based Pharmacokinetic (PBPK) models, creating a critical gap for data-driven, female-specific decision-making. To address this gap, a PBPK model extension for the FRT organs was developed in PK-Sim\/MoBi.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Physiological parameters were derived from a review of data in the public domain. The extension module characterizes four tissue compartments (cervix, vagina, endometrium, and myometrium) and two fluid compartments (uterine and cervicovaginal fluids), and enables the prediction of FRT tissue and plasma concentrations for several routes of administration, including vaginal and intra-uterine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The model\u2019s predictions for systemic and local drug administration of levonorgestrel and metronidazole were validated against clinical data, demonstrating that the module accurately captures pharmacokinetics across multiple routes of administration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The module can easily be adopted for any PBPK model in the Open Systems Pharmacology Suite. This work makes an important contribution to better representing female physiology in PBPK models and has the potential to improve women\u2019s healthcare.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1797636","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T09:38:37Z","timestamp":1782985117000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["An open-source framework for physiologically-based pharmacokinetic modeling of kinetics in the female reproductive tract"],"prefix":"10.3389","volume":"17","author":[{"given":"S.","family":"Fischer-Holzhausen","sequence":"first","affiliation":[{"name":"ESQlabs GmbH","place":["Saterland, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Nauwelaerts","sequence":"additional","affiliation":[{"name":"ESQlabs GmbH","place":["Saterland, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. 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