{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T22:47:10Z","timestamp":1789512430285,"version":"build-2803163510"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Digit. Health"],"abstract":"<jats:p>Digital twin technology, defined as dynamic digital models that represent individual patients, is emerging as a promising paradigm in precision pharmacotherapy. The integration of pharmacokinetic and pharmacodynamic (PK\/PD) modeling, clinical data, genomic information, and real-time patient monitoring enables digital twins to shift drug therapy away from population-based averages toward individualized, adaptive decisions. This narrative review explores conceptual frameworks, emerging applications, methodological approaches, clinical value, limitations, and future directions of digital twins in pharmacotherapy, with particular emphasis on the role of clinical pharmacists. Unlike broader digital twin reviews that primarily emphasize technical architectures, disease-specific applications, or pharmaceutical research and development, this review focuses on the clinical-pharmacy translation layer: how digital twin outputs can be interpreted, validated, communicated, and converted into actionable medication decisions at the bedside and across ambulatory care settings. Key applications include precision dosing, polypharmacy management, antimicrobial stewardship, and the optimization of complex therapies, alongside important ethical, regulatory, and implementation challenges.<\/jats:p>","DOI":"10.3389\/fdgth.2026.1881217","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T08:09:07Z","timestamp":1787040547000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Digital twins in precision pharmacotherapy: emerging applications, challenges, and future directions"],"prefix":"10.3389","volume":"8","author":[{"given":"Anan S.","family":"Jarab","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology","place":["Irbid, Jordan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walid","family":"Al-Qerem","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan","place":["Amman, Jordan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamza","family":"Jarab","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Jordan University of Science and Technology","place":["Irbid, Jordan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Jrab","sequence":"additional","affiliation":[{"name":"Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Zabbar","place":["Malta"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahma","family":"Elsherif","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Al Ain University","place":["Abu Dhabi, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad Z.","family":"Al Meslamani","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Al Ain University","place":["Abu Dhabi, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yazid","family":"Al Hamarneh","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine and Dentistry, University of Alberta","place":["Edmonton, AB, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salahdein","family":"Aburuz","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University","place":["Al Ain, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"25","DOI":"10.37522\/2249-1848.2024.14(4).117","article-title":"The impact of pharmacotherapy on well-being of modern health care","volume":"14","author":"Sullivan","year":"2024","journal-title":"Int J Pharm"},{"key":"B2","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1002\/wsbm.1302","article-title":"Parsing interindividual drug variability: an emerging role for systems pharmacology","volume":"7","author":"Turner","year":"2015","journal-title":"Wiley Interdiscip Rev Syst Biol Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1633539","DOI":"10.3389\/fdgth.2025.1633539","article-title":"Digital twins in healthcare: a comprehensive review and future directions","volume":"7","author":"Khoshfekr Rudsari","year":"2025","journal-title":"Front Digit Health"},{"key":"B4","doi-asserted-by":"publisher","first-page":"2042098619894147","DOI":"10.1177\/2042098619894147","article-title":"Precision dosing to avoid adverse drug reactions","volume":"10","author":"Polasek","year":"2019","journal-title":"Ther Adv Drug Saf"},{"key":"B5","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1002\/cpt.659","article-title":"Why has model-informed precision dosing not yet become common clinical reality? Lessons from the past and a roadmap for the future","volume":"101","author":"Darwich","year":"2017","journal-title":"Clin Pharmacol Ther"},{"key":"B6","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1007\/s40264-023-01387-0","article-title":"International trends in adverse drug event-related mortality from 2001 to 2019: an analysis of the world health organization mortality database from 54 countries","volume":"47","author":"Koyama","year":"2024","journal-title":"Drug Saf"},{"key":"B7","doi-asserted-by":"publisher","first-page":"511542","DOI":"10.3389\/fphar.2020.00420","article-title":"Precision dosing priority criteria: drug, disease, and patient population variables","volume":"11","author":"Tyson","year":"2020","journal-title":"Front Pharmacol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1097\/FTD.0000000000001350","article-title":"The rational basis for personalized treatment using concentration-guided dosing","volume":"47","author":"Holford","year":"2025","journal-title":"Ther Drug Monit"},{"key":"B9","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.therap.2025.09.006","article-title":"Digital pharmacological twins: bridging multi-scale modelling and artificial intelligence for precision medicine: the DIGPHAT consortium","volume":"81","author":"Woillard","year":"2026","journal-title":"Therapies"},{"key":"B10","doi-asserted-by":"publisher","first-page":"100864","DOI":"10.1016\/j.landig.2025.02.004","article-title":"Medical digital twins: enabling precision medicine and medical artificial intelligence","volume":"7","author":"Sad\u00e9e","year":"2025","journal-title":"Lancet Digit Health"},{"key":"B11","doi-asserted-by":"publisher","first-page":"101028","DOI":"10.1016\/j.patter.2024.101028","article-title":"Concepts and applications of digital twins in healthcare and medicine","volume":"5","author":"Zhang","year":"2024","journal-title":"Patterns"},{"key":"B12","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1038\/s41746-024-01073-0","article-title":"Digital twins for health: a scoping review","volume":"7","author":"Katsoulakis","year":"2024","journal-title":"npj Digit Med"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1253050","DOI":"10.3389\/fdgth.2023.1253050","article-title":"Digital twin for healthcare systems","volume":"5","author":"Vall\u00e9e","year":"2023","journal-title":"Front Digit Health"},{"key":"B14","doi-asserted-by":"publisher","first-page":"00368504251344145","DOI":"10.1177\/00368504251344145","article-title":"The computational model lifecycle: opportunities and challenges for computational medicine in the healthcare ecosystem","volume":"108","author":"Bridio","year":"2025","journal-title":"Sci Prog"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1080\/13696998.2023.2265245","article-title":"Artificial intelligence (AI) in pharmacy: an overview of innovations","volume":"26","author":"Jarab","year":"2023","journal-title":"J Med Econ"},{"key":"B16","doi-asserted-by":"publisher","first-page":"e69544","DOI":"10.2196\/69544","article-title":"Advancing health care with digital twins: meta-review of applications and implementation challenges","volume":"27","author":"Ringeval","year":"2025","journal-title":"J Med Internet Res"},{"key":"B17","doi-asserted-by":"publisher","first-page":"280","DOI":"10.3390\/ph17030280","article-title":"Pharmacokinetics and pharmacodynamics: a comprehensive analysis of the absorption, distribution, metabolism, and excretion of psychiatric drugs","volume":"17","author":"Zakaraya","year":"2024","journal-title":"Pharmaceuticals"},{"key":"B18","doi-asserted-by":"publisher","first-page":"e72411","DOI":"10.2196\/72411","article-title":"Digital twins for personalized medicine require epidemiological data and mathematical modeling: viewpoint","volume":"27","author":"Vall\u00e9e","year":"2025","journal-title":"J Med Internet Res"},{"key":"B19","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1038\/s41746-025-01447-y","article-title":"Survey and perspective on verification, validation, and uncertainty quantification of digital twins for precision medicine","volume":"8","author":"Sel","year":"2025","journal-title":"npj Digit Med"},{"key":"B20","doi-asserted-by":"publisher","first-page":"503","DOI":"10.3390\/jpm15110503","article-title":"Digital twins in personalized medicine: bridging innovation and clinical reality","volume":"15","author":"Silva","year":"2025","journal-title":"J Pers Med"},{"key":"B21","doi-asserted-by":"publisher","first-page":"2731","DOI":"10.3390\/pharmaceutics14122731","article-title":"Model-Informed precision dosing (MIPD)","volume":"14","author":"P\u00e9rez-Blanco","year":"2022","journal-title":"Pharmaceutics"},{"key":"B22","doi-asserted-by":"publisher","first-page":"115421","DOI":"10.1016\/J.ADDR.2024.115421","article-title":"Model-informed precision dosing: state of the art and future perspectives","volume":"215","author":"Minichmayr","year":"2024","journal-title":"Adv Drug Deliv Rev"},{"key":"B23","doi-asserted-by":"publisher","first-page":"534722","DOI":"10.3389\/FPHAR.2020.00620","article-title":"Software tools for model-informed precision dosing: how well do they satisfy the needs?","volume":"11","author":"Kantasiripitak","year":"2020","journal-title":"Front Pharmacol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1093\/AJHP\/ZXAA036","article-title":"Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: a revised consensus guideline and review by the American society of health-system pharmacists, the Infectious Diseases Society of America, the pediat\u2026","volume":"77","author":"Rybak","year":"2020","journal-title":"Am J Health-Syst Pharm"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.1007\/S40262-024-01414-Y","article-title":"Model-Informed precision dosing of tacrolimus: a systematic review of population pharmacokinetic models and a benchmark study of software tools","volume":"63","author":"Hoffert","year":"2024","journal-title":"Clin Pharmacokinet"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1641","DOI":"10.1038\/s41409-024-02413-0","article-title":"A practical guide to therapeutic drug monitoring in busulfan: recommendations from the pharmacist committee of the European society for blood and marrow transplantation (EBMT)","volume":"59","author":"Domingos","year":"2024","journal-title":"Bone Marrow Transplant"},{"key":"B27","doi-asserted-by":"publisher","first-page":"100021","DOI":"10.1124\/DMD.123.001384","article-title":"Utility of physiologically based pharmacokinetic modeling in predicting and characterizing clinical drug interactions","volume":"53","author":"Foti","year":"2025","journal-title":"Drug Metab Dispos"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1007\/S00134-020-06050-1","article-title":"Antimicrobial therapeutic drug monitoring in critically ill adult patients: a position paper#","volume":"46","author":"Abdul-Aziz","year":"2020","journal-title":"Intensive Care Med"},{"key":"B29","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1007\/S40265-025-02152-6","article-title":"From prospective evaluation to practice: model-informed dose optimization in oncology","volume":"85","author":"Agema","year":"2025","journal-title":"Drugs"},{"key":"B30","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1002\/CPT.1124","article-title":"Therapeutic drug monitoring in oncology: international association of therapeutic drug monitoring and clinical toxicology recommendations for 5-fluorouracil therapy","volume":"105","author":"Beumer","year":"2019","journal-title":"Clin Pharmacol Ther"},{"key":"B31","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1038\/s41746-024-01402-3","article-title":"Challenges and opportunities for digital twins in precision medicine from a complex systems perspective","volume":"8","author":"De Domenico","year":"2025","journal-title":"npj Digit Med"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1522","DOI":"10.3390\/jpm13101522","article-title":"Digital twins in healthcare: methodological challenges and opportunities","volume":"13","author":"Meijer","year":"2023","journal-title":"J Pers Med"},{"key":"B33","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1016\/j.jsps.2022.03.008","article-title":"Pharmacists\u2019 knowledge and attitudes toward medication therapy management service and the associated challenges and barriers for its implementation","volume":"30","author":"Jarab","year":"2022","journal-title":"Saudi Pharm J"},{"key":"B34","doi-asserted-by":"publisher","first-page":"2514932","DOI":"10.1080\/20565623.2025.2514932","article-title":"Utilization, perceived benefits and concerns regarding robotic technologies among community pharmacists","volume":"11","author":"Jarab","year":"2025","journal-title":"Future Sci OA"},{"key":"B35","doi-asserted-by":"publisher","first-page":"e55015","DOI":"10.2196\/55015","article-title":"Digital twins for clinical and operational decision-making scoping review","volume":"27","author":"Riahi","year":"2025","journal-title":"J Med Internet Res"},{"key":"B36","doi-asserted-by":"publisher","first-page":"950","DOI":"10.21037\/atm-22-4203","article-title":"Regulatory oversight and ethical concerns surrounding software as medical device (SaMD) and digital twin technology in healthcare","volume":"10","author":"Lal","year":"2022","journal-title":"Ann Transl Med"},{"key":"B37","author":"Ikram","year":"2025"},{"key":"B38","doi-asserted-by":"publisher","first-page":"101700","DOI":"10.1016\/j.jsps.2023.101700","article-title":"Artificial intelligence in pharmacy practice: attitude and willingness of the community pharmacists and the barriers for its implementation","volume":"31","author":"Jarab","year":"2023","journal-title":"Saudi Pharm J"},{"key":"B39","doi-asserted-by":"publisher","first-page":"8034289","DOI":"10.1155\/IJTA\/8034289","article-title":"Integrating large language models into UAE community pharmacies: pharmacists\u2019 perspectives on benefits, concerns, and implementation barriers","volume":"2026","author":"Jarab","year":"2026","journal-title":"Int J Telemed Appl"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1763","DOI":"10.3390\/healthcare13141763","article-title":"A technological review of digital twins and artificial intelligence for personalized and predictive healthcare","volume":"13","author":"Chaparro-C\u00e1rdenas","year":"2025","journal-title":"Healthcare"}],"container-title":["Frontiers in Digital Health"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fdgth.2026.1881217\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T08:09:08Z","timestamp":1787040548000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fdgth.2026.1881217\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,18]]},"references-count":40,"alternative-id":["10.3389\/fdgth.2026.1881217"],"URL":"https:\/\/doi.org\/10.3389\/fdgth.2026.1881217","relation":{},"ISSN":["2673-253X"],"issn-type":[{"value":"2673-253X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,18]]},"article-number":"1881217"}}