{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:14:48Z","timestamp":1790266488679,"version":"4.1.0"},"reference-count":68,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,10,14]],"date-time":"2015-10-14T00:00:00Z","timestamp":1444780800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP\u201086522"],"award-info":[{"award-number":["MOP\u201086522"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2016,4]]},"abstract":"Abstract<\/jats:title>Due to high basal interindividual variation in cytochrome P<\/jats:styled-content>450 3A<\/jats:styled-content> (CYP<\/jats:styled-content>3A<\/jats:styled-content>) activity and susceptibility to drug interactions, there has been interest in the application of efficient probe drug phenotyping strategies, as well as endogenous biomarkers for assessment of in vivo<\/jats:italic> CYP<\/jats:styled-content>3A<\/jats:styled-content> activity. The biomarkers 4\u03b2\u2010hydroxycholesterol (4\u03b2HC<\/jats:styled-content>) and 6\u03b2\u2010hydroxycortisol (6\u03b2HCL<\/jats:styled-content>) are sensitive to CYP<\/jats:styled-content>3A<\/jats:styled-content> induction and inhibition. However, their utility for the assessment of constitutive CYP<\/jats:styled-content>3A<\/jats:styled-content> activity remains uncertain. We investigated whether endogenous plasma biomarkers (4\u03b2HC<\/jats:styled-content> and 6\u03b2HCL<\/jats:styled-content>) are associated with basal CYP<\/jats:styled-content>3A<\/jats:styled-content> metabolic activity in healthy subjects assessed by a convenient single\u2010time\u2010point oral midazolam (MDZ<\/jats:styled-content>) phenotyping strategy. Plasma 4\u03b2HC<\/jats:styled-content> and 6\u03b2HCL<\/jats:styled-content> metabolic ratios (MR<\/jats:styled-content>s) were analysed in 51 healthy adult participants. CYP<\/jats:styled-content>3A<\/jats:styled-content> activity was determined after administration of an oral MDZ<\/jats:styled-content> microdose (100 \u03bcg). Simple linear and multiple linear regression analyses were performed to assess relationships between MDZ<\/jats:styled-content> oral clearance, biomarkers and subject covariates. Among study subjects, basal MDZ<\/jats:styled-content> oral clearance, 4\u03b2HC<\/jats:styled-content> and 6\u03b2HCL MR<\/jats:styled-content>s ranged 6.5\u2010, 10\u2010 and 13\u2010fold, respectively. Participant age and alcohol consumption were negatively associated with MDZ<\/jats:styled-content> oral clearance (p =<\/jats:italic> 0.03 and p<\/jats:italic> = 0.045, respectively), while weight and female sex were associated with lower plasma 4\u03b2HC MR<\/jats:styled-content> (p<\/jats:italic> = 0.0003 and p<\/jats:italic> = 0.032, respectively). Neither 4\u03b2HC<\/jats:styled-content> nor 6\u03b2HCL MR<\/jats:styled-content>s were associated with MDZ<\/jats:styled-content> oral clearance. Plasma 4\u03b2HC<\/jats:styled-content> and 6\u03b2HCL MR<\/jats:styled-content>s do not relate to MDZ<\/jats:styled-content> single\u2010time\u2010point metabolic phenotype in the assessment of constitutive CYP<\/jats:styled-content>3A<\/jats:styled-content> activity among healthy individuals.<\/jats:p>","DOI":"10.1111\/bcpt.12492","type":"journal-article","created":{"date-parts":[[2015,9,24]],"date-time":"2015-09-24T05:52:49Z","timestamp":1443073969000},"page":"284-291","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Relationships between Endogenous Plasma Biomarkers of Constitutive Cytochrome P<\/scp>450 3A<\/scp> Activity and Single\u2010Time\u2010Point Oral Midazolam Microdose Phenotype in Healthy Subjects"],"prefix":"10.1111","volume":"118","author":[{"given":"Sarah J.","family":"Woolsey","sequence":"first","affiliation":[{"name":"Department of Physiology & Pharmacology Schulich School of Medicine and Dentistry The University of Western Ontario London ON Canada"},{"name":"Division of Clinical Pharmacology Department of Medicine Schulich School of Medicine and Dentistry The University of Western Ontario London ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie D.","family":"Beaton","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology Department of Medicine Schulich School of Medicine and Dentistry The University of Western Ontario London ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun\u2010Hee","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Epidemiology & Biostatistics Schulich School of Medicine and Dentistry The University of Western Ontario London ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George K.","family":"Dresser","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology Department of Medicine Schulich School of Medicine and Dentistry The University of Western Ontario London ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven E.","family":"Gryn","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology Department of Medicine Schulich School of Medicine and Dentistry The University of Western Ontario London ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard B.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Physiology & Pharmacology Schulich School of Medicine and Dentistry The University of Western Ontario London ON Canada"},{"name":"Division of Clinical Pharmacology Department of Medicine Schulich School of Medicine and Dentistry The University of Western Ontario London ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rommel G.","family":"Tirona","sequence":"additional","affiliation":[{"name":"Department of Physiology & Pharmacology Schulich School of Medicine and Dentistry The University of Western Ontario London ON Canada"},{"name":"Division of Clinical Pharmacology Department of Medicine Schulich School of Medicine and Dentistry The University of Western Ontario London ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,10,14]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4757-2391-5_14"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.41.1.535"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.41.1.815"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(02)00066-2"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.38.1.389"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.111.038125"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/86882"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2010.28"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2011.336"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.09.7"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002280050420"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1989.tb03327.x"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-013-1525-5"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2044.1987.tb03086.x"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6600448"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-0023"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-011-2360-8"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2014.09.015"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(03)00056-0"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-199408000-00001"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-198428060-00002"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12502"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-200112000-00006"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-012-1437-9"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1989.tb03516.x"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2011.53"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2013.128"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12425"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2002.125559"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.31.11.1283"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M105127200"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2008.132"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.5414\/CPP47709"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2009.72"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.5414\/CPP39293"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2006.02628.x"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2009.116"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.113.052316"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.D800017-JLR200"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehs042"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2009.05285.x"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-004-0762-z"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2013.27"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.1998.tb02366.x"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.113.055475"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(99)70029-9"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2009.07.017"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-198461010-00006"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(03)00187-5"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20673"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.113.054171"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0121984"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-003-0690-3"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0b013e3282f50ee9"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920012800840464"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270008323754"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.109.031328"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.12.202"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0b013e32833225e7"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.107.018382"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.12.181"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-004-0767-7"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-008-0503-9"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2009.21"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.30.12.1491"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2014.49"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/psp.2014.18"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-014-1675-0"}],"container-title":["Basic & Clinical Pharmacology & Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbcpt.12492","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcpt.12492","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T18:36:14Z","timestamp":1696271774000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bcpt.12492"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,10,14]]},"references-count":68,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2016,4]]}},"alternative-id":["10.1111\/bcpt.12492"],"URL":"https:\/\/doi.org\/10.1111\/bcpt.12492","archive":["Portico"],"relation":{},"ISSN":["1742-7835","1742-7843"],"issn-type":[{"value":"1742-7835","type":"print"},{"value":"1742-7843","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,10,14]]},"assertion":[{"value":"2015-06-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-09-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-10-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}