{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T21:19:50Z","timestamp":1776892790231,"version":"3.51.2"},"reference-count":89,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FEDER\u2014Fundo Europeu de Desenvolimento Regional","award":["UIDB\/4255\/2020"],"award-info":[{"award-number":["UIDB\/4255\/2020"]}]},{"name":"FCT and FEDER","award":["IF\/00092\/2014\/CP1255\/CT0004"],"award-info":[{"award-number":["IF\/00092\/2014\/CP1255\/CT0004"]}]},{"name":"FCT and FEDER","award":["PRR-09\/C06-834I07\/2024.P11721"],"award-info":[{"award-number":["PRR-09\/C06-834I07\/2024.P11721"]}]},{"name":"FCT and FEDER","award":["2024.18026.PEX"],"award-info":[{"award-number":["2024.18026.PEX"]}]},{"name":"Chair in Onco-Innovation at the FMUP"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Physiologically based pharmacokinetic (PBPK) models are widely used in the context of personalized medicine, as they allow for the evaluation of dosing schedules and routes of administration by predicting absorption, distribution, metabolism and excretion (ADME) of drugs in biological systems. Traditionally, PBPK models have been developed and applied at the population level, enabling the characterization of predefined cohorts, which remains limited in supporting true precision dosing. In this review, we explored the increasingly common shift from population-based to individual PBPK modelling, where individuals are modelled as virtual twins (VTs). Through the inclusion of additional patient-specific data, such as demographic, physiological, phenotypic and genotypic information, models can be personalized, moving beyond traditional one-size-fits-all strategies. Overall, incorporating individual patient data (e.g., septic, psychiatric, cardiac, or neonatal populations) improves model performance. Physiological parameters, particularly renal function, show strong potential given their role in drug elimination, while demographic variables enhance predictive accuracy in certain studies. In contrast, the benefits of including cytochrome P450 (CYP) phenotypic and genotypic data remain inconsistent. We further emphasize methodologies used to evaluate model performance, with a focus on clinical validation through comparisons between predicted and observed concentration-time profiles. Key challenges, including limited sample sizes and data availability, that may compromise predictive precision, are also discussed. Finally, we highlight the potential integration of PBPK-based VTs into broader digital twin frameworks as a promising path toward clinical translation, while acknowledging the critical barriers that must be addressed to enable routine clinical implementation.<\/jats:p>","DOI":"10.3390\/jcm15031210","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T10:02:57Z","timestamp":1770199377000},"page":"1210","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["From Population-Based PBPK to Individualized Virtual Twins: Clinical Validation and Applications in Medicine"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6353-5184","authenticated-orcid":false,"given":"Marta","family":"Gon\u00e7alves","sequence":"first","affiliation":[{"name":"PerMed Research Group, RISE-Health, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"Laboratory of Personalized Medicine, Department of Community Medicine, Health Information and Decision (MEDCIDS), Faculty of Medicine, University of Porto, Rua Doutor Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4537-5450","authenticated-orcid":false,"given":"Pedro","family":"Barata","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, University of Fernando Pessoa, Rua Carlos da Maia, 296, 4200-150 Porto, Portugal"},{"name":"RISE-Health, Faculty of Health Sciences, University of Fernando Pessoa, Pra\u00e7a 9 de Abril, 349, 4249-004 Porto, Portugal"},{"name":"Unidade Local de Sa\u00fade de Santo Ant\u00f3nio, E.P.E., Largo Professor Abel Salazar, 4099-001 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1283-1042","authenticated-orcid":false,"given":"Nuno","family":"Vale","sequence":"additional","affiliation":[{"name":"PerMed Research Group, RISE-Health, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"Laboratory of Personalized Medicine, Department of Community Medicine, Health Information and Decision (MEDCIDS), Faculty of Medicine, University of Porto, Rua Doutor Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"RISE-Health, Department of Community Medicine, Health Information and Decision (MEDCIDS), Faculty of Medicine, University of Porto, Rua Doutor Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1146\/annurev-pharmtox-010510-100540","article-title":"Physiologically-based pharmacokinetics in drug development and regulatory science","volume":"51","author":"Rowland","year":"2011","journal-title":"Annu. 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