{"id":"https://openalex.org/W2003017820","doi":"https://doi.org/10.1067/mcp.2000.106464","title":"Significant interaction between the nonprescription antihistamine diphenhydramine and the CYP2D6 substrate metoprolol in healthy men with high or low CYP2D6 activity","display_name":"Significant interaction between the nonprescription antihistamine diphenhydramine and the CYP2D6 substrate metoprolol in healthy men with high or low CYP2D6 activity","publication_year":2000,"publication_date":"2000-05-01","ids":{"openalex":"https://openalex.org/W2003017820","doi":"https://doi.org/10.1067/mcp.2000.106464","mag":"2003017820","pmid":"https://pubmed.ncbi.nlm.nih.gov/10824625"},"language":"en","primary_location":{"id":"doi:10.1067/mcp.2000.106464","doi":"https://doi.org/10.1067/mcp.2000.106464","is_oa":false,"landing_page_url":"https://doi.org/10.1067/mcp.2000.106464","pdf_url":null,"source":{"id":"https://openalex.org/S159852663","display_name":"Clinical Pharmacology & Therapeutics","issn_l":"0009-9236","issn":["0009-9236","1085-8733","1532-6535"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-2","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320595","host_organization_name":"Wiley","host_organization_lineage":["https://openalex.org/P4310320595"],"host_organization_lineage_names":["Wiley"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Clinical Pharmacology &amp; Therapeutics","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5111775601","display_name":"Bettina A. Hamelin","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I43406934","display_name":"Universit\u00e9 Laval","ror":"https://ror.org/04sjchr03","country_code":"CA","type":"education","lineage":["https://openalex.org/I43406934"]}],"countries":["CA"],"is_corresponding":true,"raw_author_name":"B Hamelin","raw_affiliation_strings":["Faculty of Pharmacy, Laval University, Quebec Heart Institute, Laval Hospital, Sainte-Foy, Qu\u00e9bec, Canada. hamelinb@biochempharma.com","Biochem Pharma Inc, 275 Armand Frappier Blvd, Laval, Quebec, Canada H7V 4A7","Faculty of Pharmacy, Laval University, the Faculty of Medicine, Laval University, and the Quebec Heart Institute, Laval Hospital, Laval, Canada"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Faculty of Pharmacy, Laval University, Quebec Heart Institute, Laval Hospital, Sainte-Foy, Qu\u00e9bec, Canada. hamelinb@biochempharma.com","institution_ids":["https://openalex.org/I43406934"]},{"raw_affiliation_string":"Biochem Pharma Inc, 275 Armand Frappier Blvd, Laval, Quebec, Canada H7V 4A7","institution_ids":[]},{"raw_affiliation_string":"Faculty of Pharmacy, Laval University, the Faculty of Medicine, Laval University, and the Quebec Heart Institute, Laval Hospital, Laval, Canada","institution_ids":["https://openalex.org/I43406934"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5111775601"],"corresponding_institution_ids":["https://openalex.org/I43406934"],"apc_list":{"value":4410,"currency":"USD","value_usd":4410},"apc_paid":null,"fwci":4.3906,"has_fulltext":false,"cited_by_count":143,"citation_normalized_percentile":{"value":0.952138,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":88,"max":99},"biblio":{"volume":"67","issue":"5","first_page":"466","last_page":"477"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10375","display_name":"Pharmacogenetics and Drug Metabolism","score":1.0,"subfield":{"id":"https://openalex.org/subfields/3004","display_name":"Pharmacology"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10375","display_name":"Pharmacogenetics and Drug Metabolism","score":1.0,"subfield":{"id":"https://openalex.org/subfields/3004","display_name":"Pharmacology"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10570","display_name":"Drug Transport and Resistance Mechanisms","score":0.0,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11465","display_name":"Drug-Induced Hepatotoxicity and Protection","score":0.0,"subfield":{"id":"https://openalex.org/subfields/3004","display_name":"Pharmacology"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/diphenhydramine","display_name":"diphenhydramine","score":0.9990000128746033},{"id":"https://openalex.org/keywords/metoprolol","display_name":"metoprolol","score":0.9990000128746033},{"id":"https://openalex.org/keywords/cyp2d6","display_name":"CYP2D6","score":0.949999988079071},{"id":"https://openalex.org/keywords/drug-interactions","display_name":"drug interactions","score":0.777999997138977},{"id":"https://openalex.org/keywords/enzyme-inhibition","display_name":"enzyme inhibition","score":0.6850000023841858},{"id":"https://openalex.org/keywords/alpha-hydroxylation","display_name":"\u03b1-hydroxylation","score":0.847000002861023},{"id":"https://openalex.org/keywords/extensive-metabolizers","display_name":"extensive metabolizers","score":0.5889999866485596},{"id":"https://openalex.org/keywords/poor-metabolizers","display_name":"poor metabolizers","score":1.0},{"id":"https://openalex.org/keywords/pharmacokinetics","display_name":"pharmacokinetics","score":0.8939999938011169},{"id":"https://openalex.org/keywords/pharmacodynamics","display_name":"pharmacodynamics","score":0.9509999752044678},{"id":"https://openalex.org/keywords/heart-rate","display_name":"heart rate","score":0.5979999899864197},{"id":"https://openalex.org/keywords/blood-pressure","display_name":"blood pressure","score":0.871999979019165},{"id":"https://openalex.org/keywords/aortic-flow","display_name":"aortic blood flow","score":0.8080000281333923},{"id":"https://openalex.org/keywords/antihistamines","display_name":"antihistamines","score":0.7379999756813049},{"id":"https://openalex.org/keywords/over-the-counter-drugs","display_name":"over-the-counter drugs","score":0.6990000009536743}],"concepts":[{"id":"https://openalex.org/C2781280847","wikidata":"https://www.wikidata.org/wiki/Q409468","display_name":"Metoprolol","level":2,"score":0.8884474635124207},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.7446523308753967},{"id":"https://openalex.org/C2781292560","wikidata":"https://www.wikidata.org/wiki/Q413486","display_name":"Diphenhydramine","level":3,"score":0.7086721062660217},{"id":"https://openalex.org/C2776880894","wikidata":"https://www.wikidata.org/wiki/Q324089","display_name":"Antihistamine","level":2,"score":0.6475982069969177},{"id":"https://openalex.org/C33664856","wikidata":"https://www.wikidata.org/wiki/Q3271142","display_name":"CYP2D6","level":4,"score":0.5295893549919128},{"id":"https://openalex.org/C97320921","wikidata":"https://www.wikidata.org/wiki/Q718753","display_name":"Drug interaction","level":3,"score":0.5280452966690063},{"id":"https://openalex.org/C2777600422","wikidata":"https://www.wikidata.org/wiki/Q3704421","display_name":"Debrisoquine","level":5,"score":0.4556851387023926},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.44683223962783813},{"id":"https://openalex.org/C112705442","wikidata":"https://www.wikidata.org/wiki/Q323936","display_name":"Pharmacokinetics","level":2,"score":0.43523144721984863},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.4317905604839325},{"id":"https://openalex.org/C207001950","wikidata":"https://www.wikidata.org/wiki/Q141124","display_name":"In vivo","level":2,"score":0.42131859064102173},{"id":"https://openalex.org/C1122143","wikidata":"https://www.wikidata.org/wiki/Q61233","display_name":"Histamine","level":2,"score":0.33982208371162415},{"id":"https://openalex.org/C134018914","wikidata":"https://www.wikidata.org/wiki/Q162606","display_name":"Endocrinology","level":1,"score":0.3251182436943054},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.29893508553504944},{"id":"https://openalex.org/C526171541","wikidata":"https://www.wikidata.org/wiki/Q407693","display_name":"Cytochrome P450","level":3,"score":0.19232648611068726},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.1431589424610138},{"id":"https://openalex.org/C62231903","wikidata":"https://www.wikidata.org/wiki/Q1057","display_name":"Metabolism","level":2,"score":0.13742390275001526},{"id":"https://openalex.org/C150903083","wikidata":"https://www.wikidata.org/wiki/Q7108","display_name":"Biotechnology","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D000319","descriptor_name":"Adrenergic beta-Antagonists","qualifier_ui":"Q000097","qualifier_name":"blood","is_major_topic":false},{"descriptor_ui":"D000319","descriptor_name":"Adrenergic beta-Antagonists","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":true},{"descriptor_ui":"D000319","descriptor_name":"Adrenergic beta-Antagonists","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D000319","descriptor_name":"Adrenergic beta-Antagonists","qualifier_ui":"Q000652","qualifier_name":"urine","is_major_topic":false},{"descriptor_ui":"D000328","descriptor_name":"Adult","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002851","descriptor_name":"Chromatography, High Pressure Liquid","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004155","descriptor_name":"Diphenhydramine","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D004347","descriptor_name":"Drug Interactions","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006439","descriptor_name":"Hemodynamics","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D006634","descriptor_name":"Histamine H1 Antagonists","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008297","descriptor_name":"Male","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008790","descriptor_name":"Metoprolol","qualifier_ui":"Q000097","qualifier_name":"blood","is_major_topic":false},{"descriptor_ui":"D008790","descriptor_name":"Metoprolol","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":true},{"descriptor_ui":"D008790","descriptor_name":"Metoprolol","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D008790","descriptor_name":"Metoprolol","qualifier_ui":"Q000652","qualifier_name":"urine","is_major_topic":false},{"descriptor_ui":"D012016","descriptor_name":"Reference Values","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D017078","descriptor_name":"Laser-Doppler Flowmetry","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D019389","descriptor_name":"Cytochrome P-450 CYP2D6","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D019389","descriptor_name":"Cytochrome P-450 CYP2D6","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D019540","descriptor_name":"Area Under Curve","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D065690","descriptor_name":"Cytochrome P-450 CYP2D6 Inhibitors","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":3,"locations":[{"id":"doi:10.1067/mcp.2000.106464","doi":"https://doi.org/10.1067/mcp.2000.106464","is_oa":false,"landing_page_url":"https://doi.org/10.1067/mcp.2000.106464","pdf_url":null,"source":{"id":"https://openalex.org/S159852663","display_name":"Clinical Pharmacology & Therapeutics","issn_l":"0009-9236","issn":["0009-9236","1085-8733","1532-6535"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-2","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320595","host_organization_name":"Wiley","host_organization_lineage":["https://openalex.org/P4310320595"],"host_organization_lineage_names":["Wiley"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Clinical Pharmacology &amp; Therapeutics","raw_type":"journal-article"},{"id":"pmid:10824625","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/10824625","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Clinical pharmacology and therapeutics","raw_type":"Clinical Trial"},{"id":"pmh:oai:corpus.ulaval.ca:20.500.11794/69404","doi":null,"is_oa":false,"landing_page_url":"http://hdl.handle.net/20.500.11794/69404","pdf_url":null,"source":{"id":"https://openalex.org/S4306400293","display_name":"Corpus Universit\u00e9 Laval (Universit\u00e9 Laval)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I43406934","host_organization_name":"Universit\u00e9 Laval","host_organization_lineage":["https://openalex.org/I43406934"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"","raw_type":"article de recherche"}],"best_oa_location":null,"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.9940000176429749}],"study_designs":[{"id":"https://openalex.org/study-designs/clinical-trial","display_name":"Clinical Trial"}],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":46,"referenced_works":["https://openalex.org/W138220232","https://openalex.org/W1135448645","https://openalex.org/W1964139638","https://openalex.org/W1970846917","https://openalex.org/W1972572857","https://openalex.org/W1984595407","https://openalex.org/W1991468788","https://openalex.org/W1993020095","https://openalex.org/W1994834031","https://openalex.org/W1999730387","https://openalex.org/W2006803983","https://openalex.org/W2009249445","https://openalex.org/W2012610108","https://openalex.org/W2019947002","https://openalex.org/W2022866198","https://openalex.org/W2037085702","https://openalex.org/W2042117065","https://openalex.org/W2042245935","https://openalex.org/W2045157323","https://openalex.org/W2051958554","https://openalex.org/W2052085254","https://openalex.org/W2057197157","https://openalex.org/W2058040819","https://openalex.org/W2061406410","https://openalex.org/W2086968218","https://openalex.org/W2092510009","https://openalex.org/W2095042769","https://openalex.org/W2106230364","https://openalex.org/W2110464910","https://openalex.org/W2110940194","https://openalex.org/W2126226320","https://openalex.org/W2131414900","https://openalex.org/W2133290235","https://openalex.org/W2153834789","https://openalex.org/W2156047872","https://openalex.org/W2164820022","https://openalex.org/W2166202306","https://openalex.org/W2172101377","https://openalex.org/W2227274237","https://openalex.org/W2263983966","https://openalex.org/W2287022985","https://openalex.org/W2313064083","https://openalex.org/W2335911900","https://openalex.org/W2410274805","https://openalex.org/W2411107379","https://openalex.org/W2624430051"],"related_works":["https://openalex.org/W2130856625","https://openalex.org/W2501205885","https://openalex.org/W2013172494","https://openalex.org/W2081057141","https://openalex.org/W2038304491","https://openalex.org/W7009402996","https://openalex.org/W1998778273","https://openalex.org/W2072502280","https://openalex.org/W1993997822","https://openalex.org/W2145055984"],"abstract_inverted_index":{"The":[0],"prototype":[1],"\"classic\"":[2],"over-the-counter":[3],"antihistamine":[4],"diphenhydramine":[5,24,111,116,142,180,213,226,253],"was":[6,18,117,177],"shown":[7],"to":[8,20,74,99,175],"interact":[9],"with":[10,62,69,87,215,260],"the":[11,26,29,76,105,134,172,228,237,244],"polymorphic":[12],"P450":[13],"enzyme":[14],"CYP2D6.":[15],"This":[16],"project":[17],"undertaken":[19],"investigate":[21],"(1)":[22],"whether":[23,39],"inhibits":[25,227],"biotransformation":[27],"of":[28,80,107,110,122,129,137,230,243],"clinically":[30,47],"relevant":[31,247],"CYP2D6":[32,70,97,256],"substrate":[33],"metoprolol":[34,101,123,138,144,176,231],"in":[35,41,45,54,104,156,165,181,209,232],"vitro":[36,42,57],"and":[37,50,78,132,146,150,195,205,218,240,254],"(2)":[38],"this":[40],"interaction":[43,53],"results":[44],"a":[46,118,261],"significant":[48],"pharmacokinetic":[49],"pharmacodynamic":[51],"drug":[52,248],"vivo.":[55],"In":[56,114,140],"incubations":[58],"were":[59,202],"carried":[60],"out":[61],"microsomes":[63],"obtained":[64],"from":[65],"lymphoblastic":[66],"cells":[67],"transfected":[68],"complementary":[71],"deoxyribonucleic":[72],"acid":[73],"determine":[75],"type":[77],"extent":[79],"inhibition.":[81],"We":[82,223],"then":[83],"randomized":[84],"16":[85],"subjects":[86],"genetically":[88],"determined":[89],"high":[90],"(extensive":[91],"metabolizers)":[92,96],"or":[93,112],"low":[94],"(poor":[95],"activity":[98],"receive":[100],"(100":[102],"mg)":[103],"presence":[106],"steady-state":[108],"concentrations":[109],"placebo.":[113,222],"vitro,":[115],"potent":[119],"competitive":[120],"inhibitor":[121],"alpha-hydroxylation,":[124],"exhibiting":[125],"an":[126],"inhibitory":[127],"constant":[128,136],"2":[130],"micromol/L":[131],"increasing":[133],"Michaelis-Menten":[135],"sixfold.":[139],"vivo,":[141],"decreased":[143],"oral":[145],"nonrenal":[147],"clearances":[148],"twofold":[149],"metoprolol-->alpha-hydroxymetoprolol":[151],"partial":[152],"metabolic":[153],"clearance":[154],"2.5-fold":[155],"extensive":[157,210,219,233],"metabolizers":[158,167,183,211,217,220],"(all":[159],"P":[160],"<":[161],".05)":[162],"but":[163],"not":[164],"poor":[166,182,216],"(P":[168,184],">":[169,185],".2).":[170],"Although":[171],"hemodynamic":[173],"response":[174],"unaltered":[178],"by":[179],".05),":[186],"metoprolol-related":[187],"effects":[188,242],"on":[189],"heart":[190],"rate,":[191],"systolic":[192],"blood":[193,198],"pressure,":[194],"Doppler-derived":[196],"aortic":[197],"flow":[199],"peak":[200],"velocity":[201],"more":[203],"pronounced":[204],"lasted":[206],"significantly":[207],"longer":[208],"receiving":[212,221],"compared":[214],"conclude":[224],"that":[225],"metabolism":[229],"metabolizers,":[234],"thereby":[235],"prolonging":[236],"negative":[238],"chronotropic":[239],"inotropic":[241],"drug.":[245],"Clinically":[246],"interactions":[249],"may":[250],"occur":[251],"between":[252],"many":[255],"substrates,":[257],"particularly":[258],"those":[259],"narrow":[262],"therapeutic":[263],"index.":[264]},"counts_by_year":[{"year":2026,"cited_by_count":2},{"year":2025,"cited_by_count":1},{"year":2024,"cited_by_count":1},{"year":2023,"cited_by_count":5},{"year":2022,"cited_by_count":4},{"year":2021,"cited_by_count":8},{"year":2020,"cited_by_count":3},{"year":2019,"cited_by_count":2},{"year":2018,"cited_by_count":3},{"year":2017,"cited_by_count":6},{"year":2016,"cited_by_count":2},{"year":2015,"cited_by_count":4},{"year":2014,"cited_by_count":3},{"year":2013,"cited_by_count":8},{"year":2012,"cited_by_count":4}],"updated_date":"2026-11-07T11:25:07.637180","created_date":"2016-06-24T00:00:00"}
