{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T20:50:45Z","timestamp":1787086245334,"version":"build-2736575974"},"reference-count":38,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2017,7,21]],"date-time":"2017-07-21T00:00:00Z","timestamp":1500595200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006095","name":"South-Eastern Norway Regional Health Authority","doi-asserted-by":"crossref","award":["2014115"],"award-info":[{"award-number":["2014115"]}],"id":[{"id":"10.13039\/501100006095","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>4\u03b2\u2010Hydroxycholesterol (4\u03b2OHC) is sensitive towards induction or inhibition of CYP3A4, but its potential usefulness as a dosing biomarker remains to be demonstrated. The aim of this study was to investigate the correlation between 4\u03b2OHC levels and steady\u2010state concentrations (Css) of quetiapine, a CYP3A4 substrate with high presystemic metabolism, in psychiatric patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Serum samples from 151 patients treated with quetiapine as immediate release (IR; <jats:italic>n<\/jats:italic>\u00a0=\u00a098) or slow release (XR; <jats:italic>n<\/jats:italic>\u00a0=\u00a053) tablets were included for analysis of 4\u03b2OHC. In all patients, Css of quetiapine had been measured at trough level, i.e. 10\u201314 and 17\u201325\u00a0h post\u2010dosing for IR and XR tablets, respectively. Correlations between 4\u03b2OHC levels and dose\u2010adjusted Css (C\/D ratios) of quetiapine were tested by univariate (Spearman's) and multivariate (multiple linear regression) analyses. Gender, age (\u226560 <jats:italic>vs.<\/jats:italic> &lt;60 years) and tablet formulation were included as potential covariates in the multivariate analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Correlations between 4\u03b2OHC levels and quetiapine C\/D ratios were highly significant both for IR\u2010 and XR\u2010treated patients (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001). Estimated Spearman <jats:italic>r<\/jats:italic> values were \u22120.47 (95% confidence interval\u00a0\u22120.62, \u22120.30) and \u22120.56 (\u22120.72, \u22120.33), respectively. The relationship between 4\u03b2OHC level and quetiapine C\/D ratio was also significant in the multiple linear regression analysis (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001), including gender (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.023) and age (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.003) as significant covariates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The present study shows that 4\u03b2OHC level is significantly correlated with steady\u2010state concentration of quetiapine. This supports the potential usefulness of 4\u03b2OHC as a phenotype biomarker for individualized dosing of quetiapine and other drugs where systemic exposure is mainly determined by CYP3A4 metabolism.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13341","type":"journal-article","created":{"date-parts":[[2017,6,6]],"date-time":"2017-06-06T03:54:47Z","timestamp":1496721287000},"page":"2398-2405","source":"Crossref","is-referenced-by-count":22,"title":["4\u03b2\u2010Hydroxycholesterol level significantly correlates with steady\u2010state serum concentration of the CYP3A4 substrate quetiapine in psychiatric patients"],"prefix":"10.1111","volume":"83","author":[{"given":"Caroline","family":"Gjestad","sequence":"first","affiliation":[{"name":"Center for Psychopharmacology Diakonhjemmet Hospital  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tore","family":"Haslemo","sequence":"additional","affiliation":[{"name":"Center for Psychopharmacology Diakonhjemmet Hospital  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ole A.","family":"Andreassen","sequence":"additional","affiliation":[{"name":"NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine University of Oslo  Oslo Norway"},{"name":"Division of Mental Health and Addiction Oslo University Hospital  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6190-2751","authenticated-orcid":false,"given":"Espen","family":"Molden","sequence":"additional","affiliation":[{"name":"Center for Psychopharmacology Diakonhjemmet Hospital  Oslo Norway"},{"name":"Department of Pharmaceutical Biosciences, School of Pharmacy University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,7,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2012.12.007"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-200112000-00006"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-016-2178-y"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2013.00012"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.clpt.6100050"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.2133\/dmpk.DMPK-13-SH-138"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2008.03309.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2007.03078.x"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2008.132"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2009.72"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M105127200"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M201712200"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0b013e3282f50ee9"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12733"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2010.03773.x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2010.16"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12833"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-008-0492-8"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.5414\/CPP47709"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.113.052316"},{"key":"e_1_2_9_22_1","article-title":"Preparation, characterization and evaluation of quetiapine fumarate solid lipid nanoparticles to improve the oral bioavailability","volume":"2013","author":"Narala A","year":"2013","journal-title":"J Pharm"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200140070-00003"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e31821160c4"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2005.02507.x"},{"key":"e_1_2_9_26_1","unstructured":"FlockhartD.Drug interactions: cytochrome P450 drug interaction table. 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