{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T20:08:28Z","timestamp":1787170108832,"version":"build-2736575974"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,6,5]],"date-time":"2019-06-05T00:00:00Z","timestamp":1559692800000},"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":["299309"],"award-info":[{"award-number":["299309"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:p>\n                    The relevance of endogenous 4\u03b2\u2010hydroxycholesterol (4\u03b2\u2010OHC) plasma concentrations or of the 4\u03b2\u2010OHC\/total cholesterol concentration ratio (4\u03b2\u2010OHC ratio) as surrogate markers of cytochrome P450 3A (CYP3A) activity was evaluated in individuals with (\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a038) or without (\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a035) type 2 diabetes (T2D). Midazolam was used as a comparator to validate exploratory measures of phenotypic CYP3A activity. Metabolic ratios of orally administered midazolam in nondiabetic and diabetic populations correlated significantly with 4\u03b2\u2010OHC (\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>s<\/jats:sub>\n                    \u00a0=\u00a00.64 and 0.48;\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0\u2264\u00a00.003) and 4\u03b2\u2010OHC ratio (\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>s<\/jats:sub>\n                    \u00a0=\u00a00.69 and 0.46;\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0\u2264\u00a00.003), respectively. Activity of CYP3A was lower in the T2D population compared with nondiabetic subjects; this decrease was reflected in 4\u03b2\u2010OHC concentrations (24.33 vs. 12.58\u00a0ng\/mL;\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&lt;\u00a00.0001) and 4\u03b2\u2010OHC ratio (0.13 vs. 0.09 (\u00d7\u00a010\n                    <jats:sup>4<\/jats:sup>\n                    );\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&lt;\u00a00.0002). These results suggest that 4\u03b2\u2010OHC should be considered as a valid, convenient, and easy to use endogenous biomarker of CYP3A activity in patients.\n                  <\/jats:p>","DOI":"10.1002\/cpt.1472","type":"journal-article","created":{"date-parts":[[2019,4,19]],"date-time":"2019-04-19T09:48:12Z","timestamp":1555667292000},"page":"831-840","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Use of 4\u03b2\u2010Hydroxycholesterol Plasma Concentrations as an Endogenous Biomarker of CYP3A Activity: Clinical Validation in Individuals With Type 2 Diabetes"],"prefix":"10.1111","volume":"106","author":[{"given":"Sophie","family":"Gravel","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy Universit\u00e9 de Montr\u00e9al  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"CRCHUM\u2010Centre de Recherche du Centre Hospitalier de l'Universit\u00e9 de Montr\u00e9al  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Louis","family":"Chiasson","sequence":"additional","affiliation":[{"name":"CRCHUM\u2010Centre de Recherche du Centre Hospitalier de l'Universit\u00e9 de Montr\u00e9al  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"CHUM Centre Hospitalier de l'Universit\u00e9 de Montr\u00e9al  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Faculty of Medicine Universit\u00e9 of Montr\u00e9al  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fleur","family":"Gaudette","sequence":"additional","affiliation":[{"name":"CRCHUM\u2010Centre de Recherche du Centre Hospitalier de l'Universit\u00e9 de Montr\u00e9al  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Turgeon","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy Universit\u00e9 de Montr\u00e9al  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"CRCHUM\u2010Centre de Recherche du Centre Hospitalier de l'Universit\u00e9 de Montr\u00e9al  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronique","family":"Michaud","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy Universit\u00e9 de Montr\u00e9al  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"CRCHUM\u2010Centre de Recherche du Centre Hospitalier de l'Universit\u00e9 de Montr\u00e9al  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,6,5]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.116.233635"},{"key":"e_1_2_10_2_1","first-page":"414","article-title":"Interindividual variations in human liver cytochrome P\u2010450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians","volume":"270","author":"Shimada T.","year":"1994","journal-title":"J. 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