{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:04:19Z","timestamp":1790899459743,"version":"4.1.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"4","funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20GM103434"],"award-info":[{"award-number":["P20GM103434"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20RR016477"],"award-info":[{"award-number":["P20RR016477"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,5,1]]},"DOI":"10.1093\/jat\/bkw135","type":"journal-article","created":{"date-parts":[[2016,12,14]],"date-time":"2016-12-14T20:07:02Z","timestamp":1481746022000},"page":"325-333","source":"Crossref","is-referenced-by-count":37,"title":["Tell-Tale SNPs: The Role of CYP2B6 in Methadone Fatalities"],"prefix":"10.1093","volume":"41","author":[{"given":"Taha","family":"Ahmad","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, 1700 Third Avenue, Huntington, WV 25755, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samie","family":"Sabet","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, 1700 Third Avenue, Huntington, WV 25755, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald A.","family":"Primerano","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, 1700 Third Avenue, Huntington, WV 25755, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren L.","family":"Richards-Waugh","sequence":"additional","affiliation":[{"name":"Forensic Science Department, Marshall University, 1401 Forensic Science Drive, Huntington, WV 25701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary O.","family":"Rankin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, 1700 Third Avenue, Huntington, WV 25755, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,2,10]]},"reference":[{"key":"key\n\t\t\t\t20180328164256_bkw135C1","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.2217\/pgs.14.56","article-title":"Pharmacogenomics of methadone maintenance treatment","volume":"15","author":"Somogyi","year":"2014","journal-title":"Pharmacogenomics"},{"key":"key\n\t\t\t\t20180328164256_bkw135C2","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1080\/J354v19n04_05","article-title":"Pharmacokinetics of methadone","volume":"19","author":"Lugo","year":"2005","journal-title":"Journal of Pain and Palliative Care Pharmacotherapy"},{"key":"key\n\t\t\t\t20180328164256_bkw135C3","first-page":"109","article-title":"Is it time to consider use of levo-methadone (R-(-)-methadone) to replace racemic methadone","volume":"2","author":"Lisberg","year":"2013","journal-title":"Journal of Developing Drugs"},{"key":"key\n\t\t\t\t20180328164256_bkw135C4","first-page":"1353","article-title":"Methadone treatment for pain states","volume":"71","author":"Toombs","year":"2005","journal-title":"American Family Physician"},{"key":"key\n\t\t\t\t20180328164256_bkw135C5","first-page":"1155","article-title":"Chronic nonmalignant pain in primary care","volume":"78","author":"Jackman","year":"2008","journal-title":"American Family Physician"},{"key":"key\n\t\t\t\t20180328164256_bkw135C6","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1046\/j.1526-4637.2000.00027.x","article-title":"Methadone in the treatment of chronic nonmalignant pain: a 2-year follow-up","volume":"1","author":"Taylor","year":"2000","journal-title":"Pain Medicine"},{"key":"key\n\t\t\t\t20180328164256_bkw135C7","doi-asserted-by":"crossref","first-page":"e4","DOI":"10.1016\/j.jpainsymman.2008.04.007","article-title":"Methadone: a closer look at the controversy","volume":"36","author":"Gaertner","year":"2008","journal-title":"Journal of Pain Symptom Management"},{"key":"key\n\t\t\t\t20180328164256_bkw135C8","doi-asserted-by":"crossref","first-page":"171","DOI":"10.3109\/10408363.2011.620601","article-title":"Methadone: a review of drug-drug and pathophysiological interactions","volume":"48","author":"Kapur","year":"2011","journal-title":"Critical Reviews in Clinical Laboratory Sciences"},{"key":"key\n\t\t\t\t20180328164256_bkw135C9","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1111\/j.1360-0443.2011.03374.x","article-title":"R)-methadone versus racemic methadone: what is best for patient care","volume":"106","author":"McCance-Katz","year":"2011","journal-title":"Addiction"},{"key":"key\n\t\t\t\t20180328164256_bkw135C10","doi-asserted-by":"crossref","first-page":"PL 45","DOI":"10.1016\/0024-3205(94)00937-6","article-title":"The mu1, mu2, delta, kappa opioid receptor binding profiles of methadone stereoisomers and morphine","volume":"56","author":"Kristensen","year":"1995","journal-title":"Life Sciences"},{"key":"key\n\t\t\t\t20180328164256_bkw135C11","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1046\/j.1365-2125.1999.00921.x","article-title":"Methadone n-demethylation in human liver microsomes: lack of stereoselectivity and involvement of CYP3A4","volume":"47","author":"Foster","year":"1999","journal-title":"British Journal of Clinical Pharmacology"},{"key":"key\n\t\t\t\t20180328164256_bkw135C12","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1111\/j.1365-2125.2004.02221.x","article-title":"Subjective and physiological responses among racemic-methadone maintenance patients in relation to relative (S)- vs. (R)-methadone exposure","volume":"58","author":"Mitchell","year":"2004","journal-title":"British Journal of Clinical Pharmacology"},{"key":"key\n\t\t\t\t20180328164256_bkw135C13","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.resp.2009.09.001","article-title":"S-Methadone augments R-methadone induced respiratory depression in the neonatal guinea pig","volume":"169","author":"Silverman","year":"2009","journal-title":"Respiratory Physiology & Neurobiology"},{"key":"key\n\t\t\t\t20180328164256_bkw135C14","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1097\/FPC.0b013e32835cb2e2","article-title":"Contribution of CYP2B6 alleles in explaining extreme (S)-methadone plasma levels: a CYP2B6 gene resequencing study","volume":"23","author":"Dobrinas","year":"2013","journal-title":"Pharmacogenetis and Genomics"},{"key":"key\n\t\t\t\t20180328164256_bkw135C15","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1038\/sj.clpt.6100120","article-title":"Stereoselective block of hERG channel by (S)-methadone and QT interval prolongation in CYP2B6 slow metabolizers","volume":"81","author":"Eap","year":"2007","journal-title":"Clinical Pharmacology & Therapeutics"},{"key":"key\n\t\t\t\t20180328164256_bkw135C16","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1001\/archinternmed.2010.26","article-title":"Substitution of (R,S)-methadone by (R)-methadone impact on QT interval","volume":"170","author":"Ansermot","year":"2010","journal-title":"Archives of Internal Medicine"},{"key":"key\n\t\t\t\t20180328164256_bkw135C17","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.clpt.2005.08.011","article-title":"Methadone enantiomer plasma levels, CYP2B6, CYP2C19, and CYP2C9 genotypes, and response to treatment","volume":"78","author":"Crettol","year":"2005","journal-title":"Clinical Pharmacology and Therapeutics"},{"key":"key\n\t\t\t\t20180328164256_bkw135C18","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.phrs.2004.05.002","article-title":"Methadone\u2014metabolism, pharmacokinetics and interactions","volume":"50","author":"Ferrari","year":"2004","journal-title":"Pharmacological Research"},{"key":"key\n\t\t\t\t20180328164256_bkw135C19","first-page":"1008","article-title":"Free and bound enantiomers of methadone and its metabolite, EDDP in methadone maintenance treatment: relationship to dosage","volume":"12","author":"Lehotay","year":"2005","journal-title":"Clinical Biochemistry"},{"key":"key\n\t\t\t\t20180328164256_bkw135C20","first-page":"1347","article-title":"The involvement of cytochrome P450 3A4 in the N-demethylation of L-alpha-acetylmethadol (LAAM), norLAAM, and methadone","volume":"25","author":"Moody","year":"1997","journal-title":"Drug Metabolism and Disposition"},{"key":"key\n\t\t\t\t20180328164256_bkw135C21","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.bcp.2004.04.011","article-title":"Methadone metabolism by human placenta","volume":"68","author":"Nanovskaya","year":"2004","journal-title":"Biochemical Pharmacology"},{"key":"key\n\t\t\t\t20180328164256_bkw135C22","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/S0022-3565(24)29471-4","article-title":"Metabolism of methadone and levo-alpha-acetylmethadol (LAAM) by human intestinal cytochrome P450 3A4 (CYP3A4): potential contribution of intestinal metabolism to presystemic clearance and bioactivation","volume":"298","author":"Oda","year":"2001","journal-title":"Journal of Pharmacology and Experimental Therapeutics"},{"key":"key\n\t\t\t\t20180328164256_bkw135C23","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/j.1742-7843.2010.00628.x","article-title":"Stereo-selective metabolism of methadone by human liver microsomes and cDNA-expressed cytochrome P450s: a reconciliation","volume":"108","author":"Chang","year":"2010","journal-title":"Basic and Clinical Pharmacology & Toxicology"},{"key":"key\n\t\t\t\t20180328164256_bkw135C24","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1124\/dmd.31.6.742","article-title":"Involvement of CYP3A4, CYP2C8, and CYP2D6 in the metabolism of (R)- and (S)-methadone in vitro","volume":"31","author":"Wang","year":"2003","journal-title":"Drug Metabolism and Disposition"},{"key":"key\n\t\t\t\t20180328164256_bkw135C25","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1067\/mcp.2001.116793","article-title":"Pharmacokinetics and pharmacodynamics of methadone enantiomers after a single oral dose of racemate","volume":"70","author":"Boulton","year":"2001","journal-title":"Clinical Pharmacology & Therapeutics"},{"key":"key\n\t\t\t\t20180328164256_bkw135C26","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1001\/archpsyc.1997.01830200015002","article-title":"Drug abuse and addiction treatment research. The next generation","volume":"54","author":"Leshner","year":"1997","journal-title":"Archives of General Psychiatry"},{"key":"key\n\t\t\t\t20180328164256_bkw135C27","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/BF03256276","article-title":"Interindividual variability of methadone response: impact of genetic polymorphism","volume":"12","author":"Li","year":"2008","journal-title":"Molecular Diagnosis & Therapy"},{"key":"key\n\t\t\t\t20180328164256_bkw135C28","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.2174\/1568026043387070","article-title":"Pharmacogenetics of the cytochromes P450","volume":"4","author":"Daly","year":"2004","journal-title":"Current Topics in Medicinal Chemistry"},{"key":"key\n\t\t\t\t20180328164256_bkw135C29","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1038\/35015718","article-title":"Searching for genetic determinants in the new millennium","volume":"405","author":"Risch","year":"2000","journal-title":"Nature"},{"key":"key\n\t\t\t\t20180328164256_bkw135C30","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1080\/03602530902843483","article-title":"Polymorphism of human cytochrome P450 enzymes and its clinical impact","volume":"41","author":"Zhou","year":"2009","journal-title":"Drug Metabolism Reviews"},{"key":"key\n\t\t\t\t20180328164256_bkw135C31","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1517\/17425255.2012.657626","article-title":"Cytrochrome P450 variations in different ethnic populations","volume":"8","author":"McGraw","year":"2012","journal-title":"Expert Opinion on Drug Metabolism & Toxicology"},{"key":"key\n\t\t\t\t20180328164256_bkw135C32","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1097\/FPC.0b013e32833bba0e","article-title":"Functional characterization of 26 CYP2B6 allelic variants (CYP2B6.2-CYP2B6.28, except CYP2B6.22)","volume":"20","author":"Watanabe","year":"2010","journal-title":"Pharmacoenetica and Genomics"},{"key":"key\n\t\t\t\t20180328164256_bkw135C33","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1124\/jpet.104.068973","article-title":"Multiple novel nonsynonymous CYP2B6 gene polymorphisms in caucasians: demonstration of phenotypic null alleles","volume":"311","author":"Lang","year":"2004","journal-title":"The Journal of Pharmacology and Experimental Thearapeutics"},{"key":"key\n\t\t\t\t20180328164256_bkw135C34","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1097\/FPC.0b013e32835a450b","article-title":"Genome-wide association study of plasma efavirenz pharmacokinetics in AIDS clinical trials group protocols implicates several CYP2B6 variants","volume":"22","author":"Holzinger","year":"2012","journal-title":"Pharmacogenetics and Genomics"},{"key":"key\n\t\t\t\t20180328164256_bkw135C35","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1124\/dmd.111.040352","article-title":"Functional characterization of CYP2B6 allelic variants in demethylation of antimalarial artemether","volume":"39","author":"Honda","year":"2011","journal-title":"Drug Metabolism and Disposition"},{"key":"key\n\t\t\t\t20180328164256_bkw135C36","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1093\/jat\/bku091","article-title":"Fatal methadone toxicity: potential role of CYP3A4 genetic polymorphism","volume":"38","author":"Richards-Waugh","year":"2014","journal-title":"Journal of Analytical Toxicology"},{"key":"key\n\t\t\t\t20180328164256_bkw135C37","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.2165\/00003088-200241140-00003","article-title":"Interindividual variability of the clinical pharmacokinetics of methadone: implications for the treatment of opioid dependence","volume":"41","author":"Eap","year":"2002","journal-title":"Clinical Pharmacokinetics"},{"key":"key\n\t\t\t\t20180328164256_bkw135C38","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0379-0738(98)00169-8","article-title":"Cytochrome P450 2D6 (CYP2D6) genotyping on postmortem blood as a supplementary tool for interpretation of forensic toxicological results","volume":"99","author":"Druid","year":"1999","journal-title":"Forensic Science International"},{"key":"key\n\t\t\t\t20180328164256_bkw135C39","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1124\/mol.107.042861","article-title":"Improvement of cyclophosphamide activation by CYP2B6 mutants: from in silico to ex Vivo","volume":"73","author":"Nguyen","year":"2008","journal-title":"Molecular Pharmacology"},{"key":"key\n\t\t\t\t20180328164256_bkw135C40","doi-asserted-by":"crossref","DOI":"10.1155\/2013\/249642","article-title":"The effect of CYP2B6, CYP2D6, and CYP3A4 alleles on methadone binding: a molecular docking study","author":"Kamal","year":"2013","journal-title":"Journal of Chemistry"},{"key":"key\n\t\t\t\t20180328164256_bkw135C41","doi-asserted-by":"crossref","first-page":"547","DOI":"10.2217\/14622416.8.6.547","article-title":"Impact of CYP2B6 polymorphism on hepatic efavirenz metabolism in vitro","volume":"8","author":"Desta","year":"2007","journal-title":"Pharmacogenomics"},{"key":"key\n\t\t\t\t20180328164256_bkw135C42","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1124\/jpet.107.133306","article-title":"Aberrant splicing caused by single nucleotide polymorphism c.516 G>T [Q172H], a Marker of CYP2B6*6, is responsible for decreased expression and activity of CYP2B6 in liver","volume":"325","author":"Hofmann","year":"2008","journal-title":"The Journal of Pharmacology and Experimental Therapeutics"},{"key":"key\n\t\t\t\t20180328164256_bkw135C43","first-page":"1254","article-title":"Sex-based differenced in drug activity","volume":"80","author":"Whitley","year":"2009","journal-title":"American Family Physician"},{"key":"key\n\t\t\t\t20180328164256_bkw135C44","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.pharmthera.2012.12.007","article-title":"Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation","volume":"138","author":"Zanger","year":"2013","journal-title":"Pharmacology & Therapeutics"},{"key":"key\n\t\t\t\t20180328164256_bkw135C45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2013\/108902","article-title":"The Glycosylation of AGP and its associations with the binding of methadone","volume":"4","author":"Behan","year":"2013","journal-title":"BioMed Research International"},{"key":"key\n\t\t\t\t20180328164256_bkw135C46","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1007\/s00228-002-0530-x","article-title":"Age- and gender-related differences in carbohydrate concentrations of alpha1-acid glycoprotein variants and the effects of glycoforms on their drug-binding capacities","volume":"58","author":"Kishino","year":"2002","journal-title":"European Journal of Clinical Pharmacology"}],"container-title":["Journal of Analytical Toxicology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jat\/article-pdf\/41\/4\/325\/11191759\/bkw135.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T16:39:32Z","timestamp":1749832772000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jat\/article\/41\/4\/325\/2981962"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2,10]]},"references-count":46,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2017,2,10]]},"published-print":{"date-parts":[[2017,5,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jat\/bkw135","relation":{},"ISSN":["0146-4760","1945-2403"],"issn-type":[{"value":"0146-4760","type":"print"},{"value":"1945-2403","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2017,5]]},"published":{"date-parts":[[2017,2,10]]}}}