{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T19:01:41Z","timestamp":1776452501358,"version":"3.51.2"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,3,9]],"date-time":"2016-03-09T00:00:00Z","timestamp":1457481600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004572","name":"National Health and Family Planning Commission of the People's Republic of China","doi-asserted-by":"publisher","award":["201302008"],"award-info":[{"award-number":["201302008"]}],"id":[{"id":"10.13039\/501100004572","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Drug Testing and Analysis"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:p>CYP2D6 is an important member of the cytochrome P450 (CYP450) enzyme super family, with at least 100 CYP2D6 alleles being previously identified. Genetic polymorphisms of CYP2D6 significantly influence the efficacy and safety of some drugs, which might cause adverse effects and therapeutic failure. The aim of this study was to clarify the catalytic activities of 24 CYP2D6 alleles on the oxidative <jats:italic>in vitro<\/jats:italic> metabolism of methadone. Reactions were incubated with 50\u20132000\u2009 \u00b5M methadone for 30\u2009min at 37\u2009\u00b0C and terminated by cooling to \u201080\u2009\u00b0C immediately. Methadone and the major metabolite EDDP were analyzed by an ultra\u2010performance liquid chromatography tandem mass spectrometry (UPLC\u2010MS\/MS) system. Compared with wild\u2010type CYP2D6*1, most variants showed significantly altered values in V<jats:sub>max<\/jats:sub> and intrinsic clearance (V<jats:sub>max<\/jats:sub>\/K<jats:sub>m<\/jats:sub>). Only three variants (CYP2D6*88, *91 and E215K) exhibited markedly increased intrinsic clearance values, and one variant CYP2D6*94 showed no significant difference. On the other hand, the kinetic parameters of two CYP2D6 variants (CYP2D6*92 and *96) could not be determined because they had no detectable enzyme activity, whereas 18 variants exhibited significantly decreased values. To sum up, this study demonstrated that more attention should be paid in clinical administration of methadone to individuals carrying these CYP2D6 alleles. 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