{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T17:41:37Z","timestamp":1788543697493,"version":"build-2803163510"},"reference-count":19,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T00:00:00Z","timestamp":1712880000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Nicotine readily crosses the placenta to reach fetuses. However, membrane transporters, e.g., organic cation transporters (OCTs) play a role in the clearance of nicotine from the fetal to the maternal side, and this is rarely investigated clinically. In this work, we use an <jats:italic>in silico<\/jats:italic> model to simulate an <jats:italic>ex vivo<\/jats:italic> placenta perfusion experiment, which is the gold standard for measuring the transplacental permeability of compounds, including nicotine. The model consists of a system of seven ordinary differential equations (ODEs), where each equation represents the nicotine concentration in compartments that emulate the <jats:italic>ex vivo<\/jats:italic> experiment setup. The transport role of OCTs is simulated bi-directionally at the placenta\u2019s basal membrane (the fetal side). We show that the model can not only reproduce the actual <jats:italic>ex vivo<\/jats:italic> experiment results, but also predict the likely maternal and fetal nicotine concentrations when the OCT transporters are inhibited, which leads to a \u223c12% increase in fetal nicotine concentration after 2\u00a0hours of OCT modulated nicotine perfusion. In conclusion, a first <jats:italic>in silico<\/jats:italic> model is proposed in this paper that can be used to simulate some subtle features of trans-placental properties of nicotine.<\/jats:p>","DOI":"10.3389\/fphar.2024.1275467","type":"journal-article","created":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T13:41:55Z","timestamp":1712929315000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["In silico modeling for ex vivo placenta perfusion of nicotine"],"prefix":"10.3389","volume":"15","author":[{"given":"Harvey","family":"Ho","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengjie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Kurosawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Botao","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Chiba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,4,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/s0002-9378(99)70456-4","article-title":"Relationship of umbilical vein blood flow to growth parameters in the human fetus","volume":"181","author":"Barbera","year":"1999","journal-title":"Am. 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