{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T22:25:05Z","timestamp":1790461505041,"version":"4.1.0"},"reference-count":96,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Introduction: Opioids are the most commonly used analgesic drugs for acute and chronic severe pain and are metabolized in the liver via cytochrome P450 (CYP) enzymes and UDP-glucuronosyltransferases (UGTs). Methods: A narrative review of the literature was conducted by searching the PubMed database up to December 2025, with English as the only language restriction. Relevant studies were identified using the keywords \u201copioids,\u201d \u201cpharmacogenetic,\u201d \u201ccytochrome mutations,\u201d and \u201cinteractions.\u201d Results: Polymorphisms in CYP2D6 and CYP3A4 genes can affect the pharmacokinetics, clinical effect, and safety of opioids. Furthermore, enzyme induction and inhibition by concomitant drugs or compounds (herbal products or food) are sources of variability factors in drug response that may be predictable. Conclusions: This review article summarizes current evidence on the role of pharmacogenetics and opioid-related interactions, offering a framework to better understand interindividual variability in opioid response and to inform future multimodal approaches.<\/jats:p>","DOI":"10.3390\/pharmaceutics18010059","type":"journal-article","created":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T12:23:44Z","timestamp":1767356624000},"page":"59","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Role of Clinical Pharmacogenetics and Opioid Interactions in Pain Management: Current Evidence and Future Perspectives"],"prefix":"10.3390","volume":"18","author":[{"given":"Clelia","family":"Di Salvo","sequence":"first","affiliation":[{"name":"Unit of Pharmacology and Pharmacovigilance, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Valdiserra","sequence":"additional","affiliation":[{"name":"Unit of Pharmacology and Pharmacovigilance, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Balestrieri","sequence":"additional","affiliation":[{"name":"Unit of Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuditta","family":"Beucci","sequence":"additional","affiliation":[{"name":"Unit of Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Paciulli","sequence":"additional","affiliation":[{"name":"Centro Regionale di Farmacovigilanza e Dispositivovigilanza, USL Toscana Centro, 50122 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna Irene","family":"Luculli","sequence":"additional","affiliation":[{"name":"Unit of Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1677-5797","authenticated-orcid":false,"given":"Alessandro","family":"De Vita","sequence":"additional","affiliation":[{"name":"Preclinic and Osteoncology Unit, Bioscience Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0812-3959","authenticated-orcid":false,"given":"Matteo","family":"Fornai","sequence":"additional","affiliation":[{"name":"Unit of Pharmacology and Pharmacovigilance, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2661-6183","authenticated-orcid":false,"given":"Antonello","family":"Di Paolo","sequence":"additional","affiliation":[{"name":"Unit of Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Antonioli","sequence":"additional","affiliation":[{"name":"Unit of Pharmacology and Pharmacovigilance, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,1]]},"reference":[{"key":"ref_1","first-page":"31","article-title":"Opioids","volume":"177","author":"Stein","year":"2007","journal-title":"Handb. 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