{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T18:28:50Z","timestamp":1787682530443,"version":"build-2784847793"},"reference-count":25,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,1,12]],"date-time":"2024-01-12T00:00:00Z","timestamp":1705017600000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Tramadol is an important minor opioid prescribed for pain management. In this study, we analyzed the well\u2010known impact of <jats:italic>CYP2D6<\/jats:italic> genetic variation and 60 additional variants in eight candidate genes (i.e., <jats:italic>ABCG2<\/jats:italic>, <jats:italic>SLCO1B1<\/jats:italic>, <jats:italic>CYP2D6<\/jats:italic>, <jats:italic>CYP2B6<\/jats:italic>, <jats:italic>CYP2C19<\/jats:italic>, <jats:italic>CYP2C9<\/jats:italic>, <jats:italic>CYP3A5<\/jats:italic>, and <jats:italic>CYP3A4<\/jats:italic>) on tramadol efficacy and safety. Some 108 patients with pain after surgery admitted to a post\u2010anesthesia care unit (PACU) and prescribed tramadol were recruited. They were genotyped, and tramadol M1\/M2 metabolite concentrations were determined by a newly validated HPLC\u2010MS\/MS method. CYP2D6 intermediate (IM) and poor (PM) metabolizers showed lower M1 concentrations adjusted for dose\/weight at 30\u2009and 120\u2009min compared to ultrarapid (UM) and normal (NM) metabolizers (univariate <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001 and 0.020, multivariate <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001 and 0.001, unstandardized \u03b2 coefficients\u2009=\u20090.386 and 0.346, <jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090.146 and 0.120, respectively). CYP2B6 PMs (<jats:italic>n<\/jats:italic>\u2009=\u200910) were significantly related to a higher reduction in pain 30\u2009min after tramadol intake (univariate <jats:italic>p\u2009=<\/jats:italic>\u20090.038, multivariate <jats:italic>p\u2009=<\/jats:italic>\u20090.016, unstandardized \u03b2 coefficient\u2009=\u20090.224, <jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090.178), to lower PACU admission time (<jats:italic>p<\/jats:italic>\u2009=\u20090.007), and to lower incidence of adverse drug reactions (<jats:italic>p<\/jats:italic>\u2009=\u20090.038) compared to the other phenotypes. CYP3A4 IMs and PMs showed a higher prevalence of drowsiness and dizziness (<jats:italic>p<\/jats:italic>\u2009=\u20090.028 and 0.005, respectively). Our results suggest that the interaction of CYP2B6 and CYP2D6 phenotypes may be clinically relevant, pending validation of these results in large, independent cohorts. Additional research is required to clarify the impact of <jats:italic>CYP3A4<\/jats:italic> genetic variation on tramadol response.<\/jats:p>","DOI":"10.1111\/cts.13698","type":"journal-article","created":{"date-parts":[[2023,12,23]],"date-time":"2023-12-23T06:24:41Z","timestamp":1703312681000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Impact of CYP2D6 and CYP2B6 phenotypes on the response to tramadol in patients with acute post\u2010surgical pain"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9955-1130","authenticated-orcid":false,"given":"Ana","family":"Casaj\u00fas","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Department Hospital Universitario de La Princesa, Faculty of Medicine, Universidad Aut\u00f3noma de Madrid, Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP)  Madrid 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Universidad Aut\u00f3noma de Madrid, Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1660-3135","authenticated-orcid":false,"given":"Miriam","family":"Saiz\u2010Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Research Unit, Fundaci\u00f3n Burgos por la Investigaci\u00f3n de la Salud (FBIS) Hospital Universitario de Burgos  Burgos Spain"},{"name":"Department of Health Sciences University of Burgos  Burgos Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Gutierrez","sequence":"additional","affiliation":[{"name":"Anesthesia and Surgical Critical Care Department Hospital Universitario de M\u00f3stoles  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catalina","family":"Aragon\u00e9s","sequence":"additional","affiliation":[{"name":"Anesthesia and Surgical Critical Care Department Hospital Universitario de la Princesa  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3989-3910","authenticated-orcid":false,"given":"Diana","family":"Campod\u00f3nico","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department Hospital Universitario de La Princesa, Faculty of Medicine, Universidad Aut\u00f3noma de Madrid, Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ant\u00eda","family":"G\u00f3mez\u2010Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department Hospital Universitario de La Princesa, Faculty of Medicine, Universidad Aut\u00f3noma de Madrid, Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP)  Madrid 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