{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T04:44:24Z","timestamp":1791866664769,"version":"4.3.4"},"reference-count":53,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"abstract":"<jats:p>\n                    Pregnancy results in multiple physiological changes that impact drug disposition. For example, hepatic CYP3A activity and renal transporter\u2010mediated clearance increase in late pregnancy, but the time course of these changes across pregnancy is not known. Endogenous biomarkers offer a minimally invasive approach to characterize pharmacokinetic changes during pregnancy and postpartum. The goal of this study was to determine whether 6\u03b2\u2010OH\u2010cortisol formation clearance (CL\n                    <jats:sub>f,OHCOL<\/jats:sub>\n                    ) can be used as a biomarker of hepatic CYP3A activity during pregnancy. Thus, we measured cortisol, cortisone, and 6\u03b2\u2010OH\u2010cortisol in plasma and urine from 47 women during late pregnancy and postpartum and calculated the CL\n                    <jats:sub>f,OHCOL<\/jats:sub>\n                    , unbound fraction (f\n                    <jats:sub>u<\/jats:sub>\n                    ), unbound intrinsic CL\n                    <jats:sub>f<\/jats:sub>\n                    (CL\n                    <jats:sub>f,u,int,OHCOL<\/jats:sub>\n                    ), and renal clearance (CL\n                    <jats:sub>r<\/jats:sub>\n                    ). CL\n                    <jats:sub>f,OHCOL<\/jats:sub>\n                    increased 1.3\u2010fold in late pregnancy while cortisol f\n                    <jats:sub>u<\/jats:sub>\n                    decreased significantly. CL\n                    <jats:sub>f,u,int,OHCOL<\/jats:sub>\n                    increased 1.8\u2010fold, corresponding to a 2.1\u2010fold increase in hepatic CYP3A activity. The increase in CL\n                    <jats:sub>f,u,int,OHCOL<\/jats:sub>\n                    was observed in CYP3A5 expressors and in CYP3A5 nonexpressors. In late pregnancy, the increase in CL\n                    <jats:sub>r,cortisol<\/jats:sub>\n                    and CL\n                    <jats:sub>r,OHCOL<\/jats:sub>\n                    exceeded the calculated increase in filtration clearance, suggesting increased transporter\u2010mediated secretion. The decreased f\n                    <jats:sub>u<\/jats:sub>\n                    of cortisol during pregnancy was captured by a model incorporating increased expression of corticosteroid binding globulin (CBG) and increased binding affinity of cortisol to CBG. These data suggest that CL\n                    <jats:sub>f,u,int,OHCOL<\/jats:sub>\n                    is a robust biomarker of CYP3A activity during pregnancy and could be used in future studies to characterize the time course of changes in CYP3A activity across gestation and postpartum. Further, CL\n                    <jats:sub>r,cortisol<\/jats:sub>\n                    and CL\n                    <jats:sub>r,OHCOL<\/jats:sub>\n                    may be biomarkers of kidney OCT and MATE activity and could be used to evaluate kidney transporter activity during pregnancy.\n                  <\/jats:p>","DOI":"10.1002\/cpt.70519","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T03:45:57Z","timestamp":1791863157000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Unbound Intrinsic Formation Clearance of 6\u03b2\u2010Hydroxycortisol Is a Useful Biomarker of\n                    <scp>CYP3A4<\/scp>\n                    Activity during Pregnancy"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3677-5214","authenticated-orcid":false,"given":"Aurora K","family":"Authement","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmacy University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1854-1214","authenticated-orcid":false,"given":"Mary F","family":"Hebert","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Washington, School of Pharmacy  Seattle Washington USA"},{"name":"Department of Obstetrics and Gynecology University of Washington, School of Medicine  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5582-2835","authenticated-orcid":false,"given":"Emily E","family":"Fay","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of Washington, School of Medicine  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9548-3126","authenticated-orcid":false,"given":"Nina","family":"Isoherranen","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmacy University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,12]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1081\/DMR-100102338","article-title":"The human CYP3A subfamily: practical considerations*","volume":"32","author":"Wrighton S.A.","year":"2000","journal-title":"Drug Metab. 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