{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T04:49:39Z","timestamp":1782103779292,"version":"3.54.5"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100009420","name":"Varsinais-Suomen Sairaanhoitopiiri","doi-asserted-by":"publisher","award":["13821"],"award-info":[{"award-number":["13821"]}],"id":[{"id":"10.13039\/501100009420","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Tramadol is a widely used analgesic whose bioactivation to O\u2010desmethyltramadol is primarily mediated by cytochrome P450 2D6 (CYP2D6). Genetic variability and drug\u2013drug interactions affecting CYP2D6 may influence tramadol pharmacokinetics and pharmacological effects. Cyclooxygenase\u20102 inhibitors are frequently co\u2010administered with tramadol in multimodal analgesia, but their potential to affect tramadol disposition and effects remains incompletely characterised. Celecoxib has been reported to act as a weak inhibitor of CYP2D6 in\u00a0vivo. This randomised, single\u2010blind, placebo\u2010controlled crossover study evaluated the effects of 8\u2010day pretreatment with celecoxib or etoricoxib (200 and 120\u2009mg once daily, respectively), compared with placebo, on the pharmacokinetics and pharmacological effects of a single 100\u2009mg oral dose of tramadol in 12 healthy volunteers. Plasma concentrations of tramadol and O\u2010desmethyltramadol were measured, and pharmacological effects were assessed using visual analogue scales, psychomotor testing (digit symbol substitution test) and cold pressor pain models. Celecoxib pretreatment did not change tramadol exposure but reduced the formation of O\u2010desmethyltramadol, decreasing the geometric mean AUC ratio (GMR) of O\u2010desmethyltramadol to tramadol (AUC\n                    <jats:sub>m<\/jats:sub>\n                    \/AUC\n                    <jats:sub>p<\/jats:sub>\n                    ) by 24% relative to placebo (90% CI, 0.69\u20130.84;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Etoricoxib had minimal effects on tramadol exposure or metabolism (GMR 0.92; 90% CI, 0.84\u20131.02;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.13). In conclusion, celecoxib modestly inhibited the bioactivation of tramadol, but not etoricoxib. Differences in pharmacological effects were negligible.\n                  <\/jats:p>","DOI":"10.1111\/bcpt.70261","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T05:48:45Z","timestamp":1781156925000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Celecoxib and Etoricoxib on the Pharmacokinetics and Pharmacological Effects of Orally Administered Tramadol: A Randomised Controlled Trial"],"prefix":"10.1111","volume":"139","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6039-5963","authenticated-orcid":false,"given":"Tuukka","family":"Saarikoski","sequence":"first","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care University of Turku  Turku Finland"},{"name":"Division of Perioperative Services, Intensive Care and Pain Medicine Turku University Hospital  Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1225-4561","authenticated-orcid":false,"given":"Teijo I.","family":"Saari","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care University of Turku  Turku Finland"},{"name":"Division of Perioperative Services, Intensive Care and Pain Medicine Turku University Hospital  Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9577-2788","authenticated-orcid":false,"given":"Janne T.","family":"Backman","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Faculty of Medicine University of Helsinki  Helsinki Finland"},{"name":"Department of Clinical Pharmacology, HUS Diagnostic Center Helsinki University Hospital  Helsinki Finland"},{"name":"Individualized Drug Therapy Research Program, Faculty of Medicine University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4550-2189","authenticated-orcid":false,"given":"Mikko","family":"Niemi","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Faculty of Medicine University of Helsinki  Helsinki Finland"},{"name":"Department of Clinical Pharmacology, HUS Diagnostic Center Helsinki University Hospital  Helsinki Finland"},{"name":"Individualized Drug Therapy Research Program, Faculty of Medicine University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3631-9411","authenticated-orcid":false,"given":"Pertti J.","family":"Neuvonen","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Faculty of Medicine University of Helsinki  Helsinki Finland"},{"name":"Department of Clinical Pharmacology, HUS Diagnostic Center Helsinki University Hospital  Helsinki 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