{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T13:36:56Z","timestamp":1785332216556,"version":"3.55.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T00:00:00Z","timestamp":1770422400000},"content-version":"vor","delay-in-days":6,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Canadian Institutes of Health Research Project","award":["FRN PJT180361"],"award-info":[{"award-number":["FRN PJT180361"]}]},{"name":"Canadian Institutes of Health Research Team Grant: Personalized Health","award":["FRN 178435"],"award-info":[{"award-number":["FRN 178435"]}]},{"name":"Wolfe Medical Research Chair in Pharmacogenomics"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Tamoxifen is a prodrug that undergoes cytochrome P450(CYP)-mediated bioactivation to its active metabolite endoxifen, primarily due to CYP2D6. We aimed to investigate the clinical impact of CYP2D6 phenotype on the conversion of tamoxifen to endoxifen as well as the interplay of genetic variation and drug interactions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Samples were analyzed from a cohort of 932 breast cancer patients on tamoxifen therapy. CYP2D6 phenotype, tamoxifen, endoxifen, 4-hydroxytamoxifen, and N-desmethyl tamoxifen plasma concentrations and antidepressant CYP2D6 inhibitor use were analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key findings<\/jats:title>\n                    <jats:p>There was a significant effect of CYP2D6 phenotype and CYP2D6 inhibitor use on endoxifen concentrations (pinteraction\u2009&amp;lt;\u20090.05). CYP2D6 inhibition was predictive of patients who attained plasma endoxifen concentrations below the 16\u00a0nM and 9\u00a0nM threshold. CYP2D6 poor metabolizers and CYP2D6 normal or intermediate metabolizers on strong CYP2D6 inhibitors had the largest proportion of patients below an endoxifen threshold of 16 or 9\u00a0nM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Patients on tamoxifen should avoid strong CYP2D6 inhibitors as their endoxifen concentrations are similar to CYP2D6 poor metabolizers. The utility of endoxifen concentrations and which threshold to consider in clinical practice remains unclear. Ultimately, the clinical impact of mild or moderate CYP2D6 inhibitors on CYP2D6 normal or intermediate metabolizer depends on the endoxifen threshold applied.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jpp\/rgaf132","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T12:24:33Z","timestamp":1767011073000},"source":"Crossref","is-referenced-by-count":2,"title":["Observed tamoxifen drug interactions are dependent on both CYP2D6 phenotype and inhibitor potency"],"prefix":"10.1093","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9378-7815","authenticated-orcid":false,"given":"Denise N","family":"Keller","sequence":"first","affiliation":[{"name":"Pharmacy Services , London Health Sciences Centre, 339 Windermere Road, London, ON N6A 5A5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha J","family":"Medwid","sequence":"additional","affiliation":[{"name":"Department of Medicine , Western University, 1151 Richmond St, London, ON N6A 5C1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin M","family":"Legan","sequence":"additional","affiliation":[{"name":"Department of Medicine , Western University, 1151 Richmond St, London, ON N6A 5C1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ute I","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Department of Medicine , Western University, 1151 Richmond St, London, ON N6A 5C1, Canada"},{"name":"Department of Physiology and Pharmacology , Western University, 1151 Richmond St, London, ON N6A 5C1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8148-1632","authenticated-orcid":false,"given":"Richard B","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Medicine , Western University, 1151 Richmond St, London, ON N6A 5C1, Canada"},{"name":"Department of Physiology and Pharmacology , 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