{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T11:16:31Z","timestamp":1778066191353,"version":"3.51.4"},"reference-count":29,"publisher":"Wiley","issue":"5-6","license":[{"start":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T00:00:00Z","timestamp":1766188800000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biopharm &amp;amp; Drug Disp"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Tobacco is a major cause of chronic diseases such as lung cancer, cardiovascular disease, and chronic obstructive pulmonary disease worldwide. Nicotine, the primary psychoactive component in tobacco, is highly addictive and while not the primary driver of such tobacco\u2010related diseases, poses various health risks, particularly those affecting the cardiovascular and pulmonary systems. Although nicotine\u2010based therapies, such as nicotine replacement products, are widely utilized in smoking cessation efforts today, the impact of newer, tobacco delivery systems such as electronic nicotine delivery systems, or ENDS, remains uncertain and warrants continued evaluation. This study aims to develop and validate a physiologically based pharmacokinetic (PBPK) simulation model for nicotine using clinical pharmacokinetic data. The PBPK simulation model for nicotine was developed by incorporating drug\u2010specific and system\u2010specific parameters and by considering the systemic absorption, distribution, metabolism, and excretion of nicotine as well as its overall pharmacokinetic behavior on GastroPlus version 9.9. Validation of the developed PBPK model was performed by comparing predicted and observed plasma concentration\u2013time profiles and pharmacokinetic parameters from clinical studies across multiple routes of administration including intravenous infusion, bolus, and pulmonary inhalation. The resulting model accurately captured plasma nicotine concentrations, with predicted pharmacokinetic parameters (\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    ,\n                    <jats:italic>T<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    and AUCs) falling within acceptable ranges of observed values and computational average fold error values. The current model provides a practical tool to translate systemic nicotine exposure across delivery systems, support dose optimization against predefined target exposure, and quantify safety margins, thereby informing safer product design and evidence\u2010based decisions in public\u2010health regulatory science.\n                  <\/jats:p>","DOI":"10.1002\/bdd.70018","type":"journal-article","created":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T12:45:52Z","timestamp":1766234752000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Development of a Physiologically Based Pharmacokinetic (PBPK) Simulation Model for Nicotine"],"prefix":"10.1002","volume":"46","author":[{"given":"Brian","family":"Kim","sequence":"first","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences Binghamton University State University of New York  Binghamton New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung Hun","family":"Bae","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences Binghamton University State University of New York  Binghamton New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed","family":"Bashar","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences Binghamton University State University of New York  Binghamton New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bofang","family":"Yi","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences Binghamton University State University of New York  Binghamton New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad Asikur","family":"Rahman","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences Binghamton University State University of New York  Binghamton New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prince","family":"Awuah","sequence":"additional","affiliation":[{"name":"Center for Tobacco Products, Division of Nonclinical Science Office of Science U.S. Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Hartog","sequence":"additional","affiliation":[{"name":"Center for Tobacco Products, Division of Nonclinical Science Office of Science U.S. Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rony","family":"Panarsky","sequence":"additional","affiliation":[{"name":"Center for Tobacco Products, Division of Nonclinical Science Office of Science U.S. Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9268-8230","authenticated-orcid":false,"given":"Tao","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences Binghamton University State University of New York  Binghamton New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,20]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0801654"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaerosci.2017.11.014"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/11786302221149401"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2016.03.001"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1991.138"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20103\u2010540\u201069248\u20105_2"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0022\u20103565(25)33068\u20105"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2006.08.011"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102125.1985.tb02637.x"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009\u20109236(97)90124\u20107"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/ntr\/ntab265"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.57.1.3"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.4103\/0019\u20105545.74303"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm\u201023\u20101710"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2023.04.006"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010019\u201045778\u20109"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24071295"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010019\u201000741\u20109"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.4103\/0971\u20105851.151771"},{"key":"e_1_2_13_21_1","unstructured":"National Center for Chronic Disease Prevention and Health Promotion (US) Office on Smoking and Health.2016. \u201cE\u2010Cigarette Use Among Youth and Young Adults: A Report of the Surgeon General.\u201d Centers for Disease Control and Prevention (US): PMID: 30869850."},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010020\u201000960\u20105"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0022\u20103565(25)24269\u20100"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010022\u201005108\u2010y"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241914570"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms231810293"},{"issue":"2","key":"e_1_2_13_27_1","first-page":"33","article-title":"A Short Introduction to Pharmacokinetics","volume":"6","author":"Urso R.","year":"2002","journal-title":"European Review for Medical and Pharmacological Sciences"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002040050588"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0220300"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.3c02673"}],"container-title":["Biopharmaceutics &amp; Drug Disposition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdd.70018","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bdd.70018","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bdd.70018","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T14:58:19Z","timestamp":1771167499000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bdd.70018"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":29,"journal-issue":{"issue":"5-6","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/bdd.70018"],"URL":"https:\/\/doi.org\/10.1002\/bdd.70018","archive":["Portico"],"relation":{},"ISSN":["0142-2782","1099-081X"],"issn-type":[{"value":"0142-2782","type":"print"},{"value":"1099-081X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"2025-07-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"bdd.70018"}}