{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T04:19:22Z","timestamp":1792815562568,"version":"4.5.0"},"reference-count":57,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T00:00:00Z","timestamp":1718064000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2024,10]]},"abstract":"\n Methadone is a mu (\u03bc) opioid receptor agonist used clinically in adults and children to manage opioid use disorder, neonatal abstinence syndrome, and acute and chronic pain. It is typically marketed as a racemic mixture of\n R<\/jats:italic>\n \u2010 and\n S<\/jats:italic>\n \u2010enantiomers.\n R<\/jats:italic>\n \u2010methadone has 30\u2010to 50\u2010fold higher analgesic potency than\n S<\/jats:italic>\n \u2010methadone, and\n S<\/jats:italic>\n \u2010methadone has a greater adverse effect (prolongation) on the cardiac QTc interval. Methadone undergoes stereoselective metabolism. CYP2B6 is the primary enzyme responsible for catalyzing the metabolism of both enantiomers to the inactive metabolites,\n S<\/jats:italic>\n \u2010 and\n R<\/jats:italic>\n \u20102\u2010ethylidene\u20101,5\u2010dimethyl\u20103,3\u2010diphenylpyrrolidine (\n S<\/jats:italic>\n \u2010 and\n R<\/jats:italic>\n \u2010EDDP). Genetic variation in the\n CYP2B6<\/jats:italic>\n gene has been investigated in the context of implications for methadone pharmacokinetics, dose, and clinical outcomes. Most\n CYP2B6<\/jats:italic>\n variants result in diminished or loss of CYP2B6 enzyme activity, which can lead to higher plasma methadone concentrations (affecting\n S\u2010<\/jats:italic>\n more than\n R\u2010<\/jats:italic>\n methadone). However, the data do not consistently indicate that\n CYP2B6<\/jats:italic>\n \u2010based metabolic variability has a clinically significant effect on methadone dose, efficacy, or QTc prolongation. Expert analysis of the published literature does not support a change from standard methadone prescribing based on\n CYP2B6<\/jats:italic>\n genotype (updates at\n www.cpicpgx.org<\/jats:ext-link>\n ).\n <\/jats:p>","DOI":"10.1002\/cpt.3338","type":"journal-article","created":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T01:28:11Z","timestamp":1718155691000},"page":"932-938","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Clinical Pharmacogenetics Implementation Consortium Guideline for\n CYP2B6<\/i>\n Genotype and Methadone Therapy"],"prefix":"10.1002","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0737-4892","authenticated-orcid":false,"given":"Katherine M.","family":"Robinson","sequence":"first","affiliation":[{"name":"Department of Pharmacy and Therapeutics University of Pittsburgh School of Pharmacy Pittsburgh Pennsylvania 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