{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:13:16Z","timestamp":1792062796809,"version":"4.4.0"},"reference-count":36,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2007,1,1]],"date-time":"2007-01-01T00:00:00Z","timestamp":1167609600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2007,1,1]],"date-time":"2007-01-01T00:00:00Z","timestamp":1167609600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["dmd.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Drug Metabolism and Disposition"],"published-print":{"date-parts":[[2007,1]]},"DOI":"10.1124\/dmd.106.012088","type":"journal-article","created":{"date-parts":[[2006,10,5]],"date-time":"2006-10-05T00:37:19Z","timestamp":1160008639000},"page":"72-78","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":65,"title":["Identification of Human Cytochrome P450 Isozymes Involved in Diphenhydramine N-Demethylation"],"prefix":"10.1016","volume":"35","author":[{"given":"Tomoko","family":"Akutsu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaoru","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Sakurada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Ikegaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomomi","family":"Furihata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kan","family":"Chiba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1124\/dmd.106.012088_bib1","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1002\/j.1552-4604.1986.tb02946.x","article-title":"Pharmacokinetics of diphenhydramine and demethylated metabolite following intravenous and oral administration","volume":"26","author":"Blyden","year":"1986","journal-title":"J Clin Pharmacol"},{"key":"10.1124\/dmd.106.012088_bib2","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/S0022-3565(25)12826-7","article-title":"Cytochrome P450 isoform inhibitors as a tool for the investigation of metabolic reactions catalyzed by human liver microsomes","volume":"277","author":"Bourrie","year":"1996","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/dmd.106.012088_bib3","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1002\/cpt1978234375","article-title":"Correlation between plasma diphenhydramine level and sedative and antihistamine effects","volume":"23","author":"Carruthers","year":"1978","journal-title":"Clin Pharmacol Ther"},{"key":"10.1124\/dmd.106.012088_bib4","first-page":"391","article-title":"Identification of diphenhydramine (Benadryl) metabolites in human subjects","volume":"9","author":"Chang","year":"1974","journal-title":"Res Commun Chem Pathol Pharmacol"},{"key":"10.1124\/dmd.106.012088_bib5","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1254\/fpj.112.15","article-title":"Genetic polymorphism of the CYP2C subfamily","volume":"112","author":"Chiba","year":"1998","journal-title":"Nippon Yakurigaku Zasshi"},{"key":"10.1124\/dmd.106.012088_bib6","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S0065-2490(05)80006-1","article-title":"Xenobiotic-metabolizing human cells as tools for pharmacological and toxicological research","volume":"26","author":"Crespi","year":"1995","journal-title":"Adv Drug Res"},{"key":"10.1124\/dmd.106.012088_bib7","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1021\/tx960129f","article-title":"A refined substrate model for human cytochrome P450 2D6","volume":"10","author":"de Groot","year":"1997","journal-title":"Chem Res Toxicol"},{"key":"10.1124\/dmd.106.012088_bib8","first-page":"72555","article-title":"Labeling of diphenhydramine-containing drug products for over-the-counter human use. Final rule","volume":"67","year":"2002","journal-title":"Fed Regist"},{"key":"10.1124\/dmd.106.012088_bib9","doi-asserted-by":"crossref","first-page":"153","DOI":"10.2133\/dmpk.20.153","article-title":"Influence of CYP2C19 pharmacogenetic polymorphism on proton pump inhibitor-based therapeutics","volume":"20","author":"Furuta","year":"2005","journal-title":"Drug Metab Pharmacokinet"},{"key":"10.1124\/dmd.106.012088_bib10","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1124\/dmd.32.11.1279","article-title":"In vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19","volume":"32","author":"Giraud","year":"2004","journal-title":"Drug Metab Dispos"},{"key":"10.1124\/dmd.106.012088_bib11","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1097\/00005053-198509000-00010","article-title":"Idiosyncratic pharmacokinetics complicating treatment of major depression in an elderly woman","volume":"173","author":"Glassman","year":"1985","journal-title":"J Nerv Ment Dis"},{"key":"10.1124\/dmd.106.012088_bib12","first-page":"536","article-title":"In vitro characterization of cytochrome P450 2D6 inhibition by classic histamine H1 receptor antagonists","volume":"26","author":"Hamelin","year":"1998","journal-title":"Drug Metab Dispos"},{"key":"10.1124\/dmd.106.012088_bib13","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1067\/mcp.2000.106464","article-title":"Significant interaction between the nonprescription antihistamine diphenhydramine and the CYP2D6 substrate metoprolol in healthy men with high or low CYP2D6 activity","volume":"67","author":"Hamelin","year":"2000","journal-title":"Clin Pharmacol Ther"},{"issue":"Suppl 1","key":"10.1124\/dmd.106.012088_bib14","first-page":"91","article-title":"Multiple cytochrome P450 enzymes and FMO1 are implicated in the metabolism of diphenhydramine","volume":"33","author":"Hamelin","year":"2001","journal-title":"Drug Metab Rev"},{"key":"10.1124\/dmd.106.012088_bib15","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1007\/s00228-001-0399-0","article-title":"Inhibitory effects of H1-antihistamines on CYP2D6- and CYP2C9-mediated drug metabolic reactions in human liver microsomes","volume":"57","author":"He","year":"2002","journal-title":"Eur J Clin Pharmacol"},{"issue":"Suppl 3","key":"10.1124\/dmd.106.012088_bib16","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1046\/j.1365-2222.1999.0290s3133.x","article-title":"Antihistamines: models to assess sedative properties, assessment of sedation, safety and other side-effects","volume":"29","author":"Hindmarch","year":"1999","journal-title":"Clin Exp Allergy"},{"key":"10.1124\/dmd.106.012088_bib17","first-page":"281","article-title":"Impact of sedating antihistamines on safety and productivity","volume":"22","author":"Kay","year":"2001","journal-title":"Allergy Asthma Proc"},{"key":"10.1124\/dmd.106.012088_bib18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.clpt.2004.08.009","article-title":"Clinical consequences of cytochrome P450 2C9 polymorphisms","volume":"77","author":"Kirchheiner","year":"2005","journal-title":"Clin Pharmacol Ther"},{"key":"10.1124\/dmd.106.012088_bib19","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/S0090-9556(24)15234-8","article-title":"Involvement of CYP2E1 as a low-affinity enzyme in phenacetin O-deethylation in human liver microsomes","volume":"27","author":"Kobayashi","year":"1999","journal-title":"Drug Metab Dispos"},{"key":"10.1124\/dmd.106.012088_bib20","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1016\/S0022-3565(24)36731-X","article-title":"Reappraisal of human CYP isoforms involved in imipramine N-demethylation and 2-hydroxylation: a study using microsomes obtained from putative extensive and poor metabolizers of S-mephenytoin and eleven recombinant human CYPs","volume":"281","author":"Koyama","year":"1997","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/dmd.106.012088_bib21","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1021\/tx00026a010","article-title":"A predictive model for substrates of cytochrome P450-debrisoquine (2D6)","volume":"5","author":"Koymans","year":"1992","journal-title":"Chem Res Toxicol"},{"key":"10.1124\/dmd.106.012088_bib22","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1097\/00004714-200104000-00009","article-title":"Diphenhydramine alters the disposition of venlafaxine through inhibition of CYP2D6 activity in humans","volume":"21","author":"Lessard","year":"2001","journal-title":"J Clin Psychopharmacol"},{"key":"10.1124\/dmd.106.012088_bib23","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/S0022-3565(25)07849-8","article-title":"The anti-histamine properties of Benadryl, beta-dimethylaminoethyl benzhydryl ether hydrochloride","volume":"86","author":"Loew","year":"1946","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/dmd.106.012088_bib24","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.forsciint.2005.03.011","article-title":"A method for screening for various sedative-hypnotics in serum by liquid chromatography\/single quadrupole mass spectrometry","volume":"157","author":"Miyaguchi","year":"2006","journal-title":"Forensic Sci Int"},{"key":"10.1124\/dmd.106.012088_bib25","series-title":"Today\u2019s Drug Therapy","first-page":"301","article-title":"Antihistamines","author":"Mizushima","year":"2006"},{"key":"10.1124\/dmd.106.012088_bib26","doi-asserted-by":"crossref","first-page":"2788","DOI":"10.1001\/jama.1990.03450210088038","article-title":"Torsades de pointes occurring in association with terfenadine use","volume":"264","author":"Monahan","year":"1990","journal-title":"J Am Med Assoc"},{"key":"10.1124\/dmd.106.012088_bib27","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1097\/00008571-199610000-00009","article-title":"CYP2D6 is the principal cytochrome P450 responsible for metabolism of the histamine H1 antagonist promethazine in human liver microsomes","volume":"6","author":"Nakamura","year":"1996","journal-title":"Pharmacogenetics"},{"key":"10.1124\/dmd.106.012088_bib28","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/S0022-3565(24)37273-8","article-title":"Oxidation of histamine H1 antagonist mequitazine is catalyzed by cytochrome P450 2D6 in human liver microsomes","volume":"284","author":"Nakamura","year":"1998","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/dmd.106.012088_bib29","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S0378-4274(01)00510-0","article-title":"Cardiotoxicity of new antihistamines and cisapride","volume":"127","author":"Paakkari","year":"2002","journal-title":"Toxicol Lett"},{"key":"10.1124\/dmd.106.012088_bib30","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1080\/004982598238886","article-title":"Inhibition and induction of human cytochrome P450 (CYP) enzymes","volume":"28","author":"Pelkonen","year":"1998","journal-title":"Xenobiotica"},{"key":"10.1124\/dmd.106.012088_bib31","doi-asserted-by":"crossref","first-page":"105","DOI":"10.2174\/1389200033489523","article-title":"Classic histamine H1 receptor antagonists: a critical review of their metabolic and pharmacokinetic fate from bird\u2019s eye view","volume":"4","author":"Sharma","year":"2003","journal-title":"Curr Drug Metab"},{"key":"10.1124\/dmd.106.012088_bib32","first-page":"197","article-title":"Interaction of smoking, uptake of polycyclic aromatic hydrocarbons, and cytochrome P450IA2 activity among foundry workers","volume":"49","author":"Sherson","year":"1992","journal-title":"Br J Ind Med"},{"key":"10.1124\/dmd.106.012088_bib33","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1016\/0006-2952(92)90333-E","article-title":"Speculations of the substrate structure-activity relationship (SSAR) of cytochrome P450 enzymes","volume":"44","author":"Smith","year":"1992","journal-title":"Biochem Pharmacol"},{"key":"10.1124\/dmd.106.012088_bib34","first-page":"337","article-title":"H1-antihistamines and the central nervous system","volume":"17","author":"Welch","year":"2002","journal-title":"Clin Allergy Immunol"},{"key":"10.1124\/dmd.106.012088_bib35","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1046\/j.1365-2125.2002.01578.x","article-title":"The roles of CYP2D6 and stereoselectivity in the clinical pharmacokinetics of chlorpheniramine","volume":"53","author":"Yasuda","year":"2001","journal-title":"Br J Clin Pharmacol"},{"key":"10.1124\/dmd.106.012088_bib36","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s00210-003-0832-2","article-title":"Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry","volume":"369","author":"Zanger","year":"2004","journal-title":"Naunyn-Schmiedeberg\u2019s Arch Pharmacol"}],"container-title":["Drug Metabolism and Disposition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0090955624011814?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0090955624011814?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1124\/dmd.106.012088","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T15:14:20Z","timestamp":1739891660000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0090955624011814"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,1]]},"references-count":36,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2007,1]]}},"alternative-id":["S0090955624011814"],"URL":"https:\/\/doi.org\/10.1124\/dmd.106.012088","relation":{},"ISSN":["0090-9556"],"issn-type":[{"value":"0090-9556","type":"print"}],"subject":[],"published":{"date-parts":[[2007,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Identification of Human Cytochrome P450 Isozymes Involved in Diphenhydramine N-Demethylation","name":"articletitle","label":"Article Title"},{"value":"Drug Metabolism and Disposition","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1124\/dmd.106.012088","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2007 The American Society for Pharmacology and Experimental Therapeutics","name":"copyright","label":"Copyright"}]}}