{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T09:28:45Z","timestamp":1766050125473,"version":"build-2065373602"},"reference-count":22,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T00:00:00Z","timestamp":1662681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FEDER\u2014Fundo Europeu de Desenvolimento Regional through the COMPETE 2020\u2014Operational Programme for Competitiveness and Internationalization (POCI), Portugal 2020","award":["UIDB\/4255\/2020","IF\/00092\/2014\/CP1255\/CT0004"],"award-info":[{"award-number":["UIDB\/4255\/2020","IF\/00092\/2014\/CP1255\/CT0004"]}]},{"name":"Portuguese funds through FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia, in a framework of the projects in CINTESIS, R&amp;D Unit","award":["UIDB\/4255\/2020","IF\/00092\/2014\/CP1255\/CT0004"],"award-info":[{"award-number":["UIDB\/4255\/2020","IF\/00092\/2014\/CP1255\/CT0004"]}]},{"name":"project \u201cRISE\u2014LA\/P\/0053\/2020\u201d","award":["UIDB\/4255\/2020","IF\/00092\/2014\/CP1255\/CT0004"],"award-info":[{"award-number":["UIDB\/4255\/2020","IF\/00092\/2014\/CP1255\/CT0004"]}]},{"name":"FCT and FEDER (European Union)","award":["UIDB\/4255\/2020","IF\/00092\/2014\/CP1255\/CT0004"],"award-info":[{"award-number":["UIDB\/4255\/2020","IF\/00092\/2014\/CP1255\/CT0004"]}]},{"name":"CHAIR in Onco-Innovation at FMUP","award":["UIDB\/4255\/2020","IF\/00092\/2014\/CP1255\/CT0004"],"award-info":[{"award-number":["UIDB\/4255\/2020","IF\/00092\/2014\/CP1255\/CT0004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Nebivolol (NEB) is a highly selective \u03b21 receptor antagonist with a distinct pharmacological profile. This drug is approved for the treatment of hypertension in the US, and hypertension and heart failure in Europe. Here, we review observations based on age dependence and explore new drug regimens with in-silico studies, to achieve better efficacy and safety. The clinical data were obtained from six published literature reports. Then the data were used for model building, evaluation, and simulation. A two-compartment model with first-order absorption, lag time, linear elimination, and the following covariates: age and genotype were the ones best describing our population. Simulation of different dose regimens resulted in an increase chance of efficacy and safety when the dose regimen was altered to 6 mg every 36 h. It is worth noting that our population in this study constituted of young and healthy individuals. Studies regarding the effects of NEB according to age are scarce; however, they are needed to further improve efficacy and safety, and reduce adverse effects.<\/jats:p>","DOI":"10.3390\/pharmaceutics14091911","type":"journal-article","created":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T04:05:41Z","timestamp":1663041941000},"page":"1911","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["New Data for Nebivolol after In Silico PK Study: Focus on Young Patients and Dosage Regimen"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7003-4957","authenticated-orcid":false,"given":"Lara","family":"Marques","sequence":"first","affiliation":[{"name":"OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Dr. Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"CINTESIS@RISE, Faculty of Medicine, University of Porto, Al. Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"given":"B\u00e1rbara","family":"Costa","sequence":"additional","affiliation":[{"name":"OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Dr. Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"CINTESIS@RISE, Faculty of Medicine, University of Porto, Al. Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1283-1042","authenticated-orcid":false,"given":"Nuno","family":"Vale","sequence":"additional","affiliation":[{"name":"OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Dr. Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"CINTESIS@RISE, Faculty of Medicine, University of Porto, Al. Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"Department of Community Medicine, Health Information and Decision (MEDCIDS), Faculty of Medicine, University of Porto, Rua Dr. Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1007\/s40265-015-0435-5","article-title":"A Review of Nebivolol Pharmacology and Clinical Evidence","volume":"75","author":"Fongemie","year":"2015","journal-title":"Drugs"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1517\/14656566.5.4.893","article-title":"Nebivolol: A Review","volume":"5","author":"Cockcroft","year":"2004","journal-title":"Expert Opin. 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Drug Approval Package: Nebivolol NDA #021742, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2007\/021742s000TOC.cfm.","key":"ref_6"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.bpa.2011.08.006","article-title":"In Silico Modelling of Physiologic Systems","volume":"25","author":"Colquitt","year":"2011","journal-title":"Best Pract. Res. Clin. Anaesthesiol."},{"unstructured":"Rohatgi, A. (2022, April 11). WebPlotDigitizer\u2014Extract Data from Plots, Images, and Maps. Available online: https:\/\/automeris.io\/WebPlotDigitizer\/.","key":"ref_8"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e130","DOI":"10.1097\/MJT.0000000000000247","article-title":"A Single-Center, Open-Label, 3-Way Crossover Trial to Determine the Pharmacokinetic and Pharmacodynamic Interaction between Nebivolol and Valsartan in Healthy Volunteers at Steady State","volume":"22","author":"Chen","year":"2015","journal-title":"Am. J. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1111\/jcpt.12180","article-title":"A Pharmacokinetic Drug Interaction Study between Nebivolol and Paroxetine in Healthy Volunteers","volume":"39","author":"Briciu","year":"2014","journal-title":"J. Clin. Pharm. 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Heart J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1161\/HYPERTENSIONAHA.119.13820","article-title":"Investigation and Treatment of High Blood Pressure in Young People: Too Much Medicine or Appropriate Risk Reduction?","volume":"75","author":"Hinton","year":"2020","journal-title":"Hypertens"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1111\/jcpt.13155","article-title":"Influence of CYP2D6*5 and *10 Polymorphism on the Pharmacokinetics of Nebivolol in Healthy Chinese Subjects","volume":"45","author":"Guo","year":"2020","journal-title":"J. Clin. Pharm. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1111\/jch.12169","article-title":"Nebivolol Monotherapy in Younger Adults (Younger than 55 Years) with Hypertension: A Randomized, Placebo-Controlled Trial","volume":"15","author":"Giles","year":"2013","journal-title":"J. Clin. 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Dis."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/9\/1911\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:28:12Z","timestamp":1760142492000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/9\/1911"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,9]]},"references-count":22,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["pharmaceutics14091911"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics14091911","relation":{},"ISSN":["1999-4923"],"issn-type":[{"type":"electronic","value":"1999-4923"}],"subject":[],"published":{"date-parts":[[2022,9,9]]}}}