{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T17:42:37Z","timestamp":1774633357630,"version":"3.50.1"},"reference-count":24,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,3,20]],"date-time":"2022-03-20T00:00:00Z","timestamp":1647734400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004569","name":"Ministry of Science and Higher Education","doi-asserted-by":"publisher","award":["0305\/DLG\/2018\/10"],"award-info":[{"award-number":["0305\/DLG\/2018\/10"]}],"id":[{"id":"10.13039\/501100004569","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Antazoline is an antihistaminic drug that is effective in the termination of paroxysmal atrial fibrillation. Despite its long presence in the market, antazoline\u2019s ADME parameters and pharmacokinetic effects in humans are poorly characterized. The objective of this study was to fill this gap by generation of in vitro and in vivo data and the development of a physiologically based pharmacokinetic model describing antazoline and its main metabolite disposition. A set of ADME parameters for the antazoline and its hydroxy metabolite is provided based on literature data, QSAR predictions, in vitro binding and metabolic stability assays. These can be used to feed PBPK models. In our current work, the developed PBPK model simulating simultaneously the pharmacokinetic profile of antazoline and its metabolite was successfully verified against the available clinical data and the presented capability to account for the clinically observed variability. When used to feed the PD model (e.g., simulating ECG), concentration-time profiles predicted by the model enable the assessment of antazoline\u2019s effect in various clinical scenarios with the possibility to account for population differences or CP mediated drug-drug interactions.<\/jats:p>","DOI":"10.3390\/ph15030379","type":"journal-article","created":{"date-parts":[[2022,3,20]],"date-time":"2022-03-20T21:34:27Z","timestamp":1647812067000},"page":"379","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Development and Performance Verification of the PBPK Model for Antazoline and Its Metabolite and Its Utilization for Pharmacological Hypotheses Formulating"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4740-7903","authenticated-orcid":false,"given":"Barbara","family":"Wi\u015bniowska","sequence":"first","affiliation":[{"name":"Department of Social Pharmacy, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krak\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2567-4453","authenticated-orcid":false,"given":"Joanna","family":"Giebu\u0142towicz","sequence":"additional","affiliation":[{"name":"Department of Bioanalysis and Drugs Analysis, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8034-4898","authenticated-orcid":false,"given":"Roman","family":"Piotrowski","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Centre of Postgraduate Medical Education, Grochowski Hospital, 04-073 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piotr","family":"Ku\u0142akowski","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Centre of Postgraduate Medical Education, Grochowski Hospital, 04-073 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8614-0642","authenticated-orcid":false,"given":"Sebastian","family":"Polak","sequence":"additional","affiliation":[{"name":"Department of Social Pharmacy, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krak\u00f3w, Poland"},{"name":"Simcyp Division, Certara UK Limited, Level 2-Acero, 1 Concourse Way, Sheffield S1 2BJ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e12441","DOI":"10.1111\/anec.12441","article-title":"Antazoline-Insights into Drug-Induced Electrocardiographic and Hemodynamic Effects: Results of the ELEPHANT II Substudy","volume":"22","author":"Piotrowski","year":"2017","journal-title":"Ann. 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