{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T01:26:31Z","timestamp":1777253191791,"version":"3.51.4"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T00:00:00Z","timestamp":1607990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["1UH3TR000963"],"award-info":[{"award-number":["1UH3TR000963"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["ZIA-DA000635"],"award-info":[{"award-number":["ZIA-DA000635"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["ZIA-AA000218"],"award-info":[{"award-number":["ZIA-AA000218"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,6,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>A physiologically based pharmacokinetic (PBPK) modeling approach was used to simulate the concentration-time profile of ethanol (EtOH) in stomach, duodenum, plasma and other tissues upon consumption of beer and whiskey under fasted and fed conditions.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A full PBPK model was developed for EtOH using the advanced dissolution, absorption and metabolism (ADAM) model fully integrated into the Simcyp Simulator\u00ae 15 (Simcyp Ltd., Sheffield, UK). The prediction performance of the developed model was verified and the EtOH concentration-time profile in different organs was predicted.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Simcyp simulation showed \u2264\u20092-fold difference in values of EtOH area under the concentration-time curve (AUC) in stomach and duodenum as compared to the observed values. Moreover, the simulated EtOH maximum concentration (Cmax), time to reach Cmax (Tmax) and AUC in plasma were comparable to the observed values. We showed that liver is exposed to the highest EtOH concentration, faster than other organs (Cmax\u00a0=\u00a0839.50\u00a0mg\/L and Tmax\u00a0=\u00a00.53\u00a0h), while brain exposure of EtOH (AUC\u00a0=\u00a01139.43\u00a0mg\u00b7h\/L) is the highest among all other organs. Sensitivity analyses (SAs) showed direct proportion of EtOH rate and extent of absorption with administered EtOH dose and inverse relationship with gastric emptying time (GE) and steady-state volume of distribution (Vss).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The current PBPK model approach might help with designing in vitro experiments in the area of alcohol organ damage or alcohol-drug interaction studies.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/alcalc\/agaa129","type":"journal-article","created":{"date-parts":[[2020,11,7]],"date-time":"2020-11-07T20:10:08Z","timestamp":1604779808000},"page":"401-414","source":"Crossref","is-referenced-by-count":7,"title":["Development of a Physiologically Based Pharmacokinetic Model for Prediction of Ethanol Concentration-Time Profile in Different Organs"],"prefix":"10.1093","volume":"56","author":[{"given":"Armin","family":"Sadighi","sequence":"first","affiliation":[{"name":"Clinical Pharmacokinetics Research Laboratory , Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, 7 Greenhouse Road, Kingston, RI 02881, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenzo","family":"Leggio","sequence":"additional","affiliation":[{"name":"Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology , National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse, 10 Center Drive (10CRC\/15330), Bethesda, MD 20892, USA"},{"name":"Medication Development Program, National Institute on Drug Abuse Intramural Research Program , 251 Bayview Blvd., Baltimore, MD 21224, USA"},{"name":"Center for Alcohol and Addiction Studies , Department of Behavioral and Social Sciences, , 121 South Main Street, Providence, RI 02912, USA"},{"name":"Brown University , Department of Behavioral and Social Sciences, , 121 South Main Street, Providence, RI 02912, USA"},{"name":"Division of Addiction Medicine , Department of Medicine, School of Medicine, , Baltimore, MD, USA"},{"name":"Johns Hopkins University , Department of Medicine, School of Medicine, , Baltimore, MD, USA"},{"name":"Department of Neuroscience, Georgetown University Medical Center , 4000 Reservoir Road, Washington D.C., DC 20007, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatemeh","family":"Akhlaghi","sequence":"additional","affiliation":[{"name":"Clinical Pharmacokinetics Research Laboratory , Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, 7 Greenhouse Road, Kingston, RI 02881, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,12,15]]},"reference":[{"key":"2023101115492530800_ref1","doi-asserted-by":"crossref","first-page":"492","DOI":"10.5694\/j.1326-5377.2004.tb06407.x","article-title":"Warfarin reversal: Consensus guidelines, on behalf of the Australasian Society of Thrombosis and Haemostasis","volume":"181","author":"Baker","year":"2004","journal-title":"Med J Aust"},{"key":"2023101115492530800_ref2","doi-asserted-by":"crossref","first-page":"e202","DOI":"10.2741\/931","article-title":"Fatty acid ethyl esters: Toxic non-oxidative metabolites of ethanol and markers of ethanol intake","volume":"8","author":"Best","year":"2003","journal-title":"Front Biosci"},{"key":"2023101115492530800_ref3","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1124\/dmd.117.076463","article-title":"Age-dependent protein abundance of cytosolic alcohol and aldehyde dehydrogenases in human liver","volume":"45","author":"Bhatt","year":"2017","journal-title":"Drug Metab Dispos"},{"key":"2023101115492530800_ref4","doi-asserted-by":"crossref","first-page":"77","DOI":"10.5001\/omj.2011.21","article-title":"Food-drug interactions","volume":"26","author":"Bushra","year":"2011","journal-title":"Oman Med J"},{"key":"2023101115492530800_ref5","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.cld.2012.08.002","article-title":"Alcohol metabolism","volume":"16","author":"Cederbaum","year":"2012","journal-title":"Clin Liver Dis"},{"key":"2023101115492530800_ref6","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.cbi.2016.08.014","article-title":"Ethanol oxidation and the inhibition by drugs in human liver, stomach and small intestine: Quantitative assessment with numerical organ modeling of alcohol dehydrogenase isozymes","volume":"258","author":"Chi","year":"2016","journal-title":"Chem Biol Interact"},{"key":"2023101115492530800_ref7","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1172\/JCI113875","article-title":"Genotypes for aldehyde dehydrogenase deficiency and alcohol sensitivity. 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