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During this time, the use of opioids and other drugs can lead to drug\u2013drug interactions (DDIs), potentially resulting in adverse drug reactions (ADRs) that increase morbidity, mortality, and healthcare costs. This study investigates the drug\u2013drug interactions (DDIs) between rocuronium, propofol, paracetamol, and lidocaine, focusing on the CYP-mediated metabolism of these drugs in the perioperative context, where these drugs are frequently co-administered. Using physiologically based pharmacokinetic (PBPK) modeling through the GastroPlus\u2122 software and in vitro experiments with Hep G2 cells, we aimed to assess potential toxicities and pharmacokinetic interactions. Cellular viability assays revealed significant toxicity when lidocaine was combined with propofol and rocuronium, while paracetamol exhibited no considerable impact on viability. PBPK simulations confirmed moderate interactions with rocuronium and weak interactions with propofol but no relevant interactions with paracetamol. These findings emphasize the need for dose adjustments in perioperative settings to enhance patient safety, particularly with propofol and rocuronium, while supporting the co-administration of lidocaine and paracetamol. These findings show the importance of moving towards a personalized medicine model, adjusting the clinical use of lidocaine according to individual patient needs, thus promoting safer and more effective perioperative care and moving beyond the \u201cone-size-fits-all\u201d approach in anesthetic management.<\/jats:p>","DOI":"10.3390\/ijms26041506","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T05:34:32Z","timestamp":1739252072000},"page":"1506","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Molecular Precision Medicine: Application of Physiologically Based Pharmacokinetic Modeling to Predict Drug\u2013Drug Interactions Between Lidocaine and Rocuronium\/Propofol\/Paracetamol"],"prefix":"10.3390","volume":"26","author":[{"given":"Abigail","family":"Silva","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\/0000-0002-3062-0281","authenticated-orcid":false,"given":"Joana","family":"Mour\u00e3o","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"RISE-Health, Surgery and Physiology Department, Faculty of Medicine, University of Porto, Rua Doutor Pl\u00e1cido da Costa, 4200-450 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":[[2025,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"138","DOI":"10.7861\/fhj.2022-0051","article-title":"Perioperative medicine","volume":"9","author":"Wall","year":"2022","journal-title":"Future Healthc. 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