{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T11:39:52Z","timestamp":1774697992484,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,1,7]],"date-time":"2024-01-07T00:00:00Z","timestamp":1704585600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>A less invasive evaluation method of cytochrome P450 3A (CYP3A) activity provides an important tool for personalized medicine. We aimed to clarify the usefulness of the plasma 6\u03b2\u2010hydroxycortisol to cortisol concentration (6\u03b2\u2010OHF\/F) ratio as a minimally invasive CYP3A phenotyping method.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Plasma 6\u03b2\u2010OHF and cortisol concentrations were measured via liquid chromatography\/tandem mass spectrometry. The plasma 6\u03b2\u2010OHF\/F ratio was compared with 6\u03b2\u2010hydroxylation clearance of endogenous cortisol (CL<jats:sub>m(6\u03b2)<\/jats:sub>; which we previously developed as an index of CYP3A activity) before, during and after oral contraceptive administration in 3 healthy women. The plasma 6\u03b2\u2010OHF\/F ratio was observed during oral clarithromycin administration. The plasma 6\u03b2\u2010OHF\/F ratio was also measured in 39 healthy participants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The plasma 6\u03b2\u2010OHF\/F ratio in 3 healthy women on Day 21 of starting oral contraceptive administration decreased by 39, 49 and 61% compared with Day 0. These values were similar to CL<jats:sub>m(6\u03b2)<\/jats:sub> values (43, 54 and 59%, respectively). Plasma 6\u03b2\u2010OHF\/F ratio and CL<jats:sub>m(6\u03b2)<\/jats:sub> exhibited a good correlation (<jats:italic>r<\/jats:italic>\u2009=\u2009.9053). The 6\u03b2\u2010OHF\/F ratio decreased from 0.00921 to 0.00577 only 3\u00a0h following clarithromycin administration. The plasma 6\u03b2\u2010OHF\/F ratio ranged 0.00565\u20130.01556 in 39 healthy participants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Based on its close relationship with CL<jats:sub>m(6\u03b2)<\/jats:sub> and its decrease upon inhibition by clarithromycin, the plasma 6\u03b2\u2010OHF\/F ratio serves as an index of CYP3A activity. Using this minimally invasive index, we can identify patients with extremely low CYP3A activity before treatment initiation and optimize the initial drug dose, thereby mitigating the risk of severe adverse reactions.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.15987","type":"journal-article","created":{"date-parts":[[2023,12,16]],"date-time":"2023-12-16T09:20:51Z","timestamp":1702718451000},"page":"1016-1026","source":"Crossref","is-referenced-by-count":7,"title":["Plasma 6\u03b2\u2010hydroxycortisol to cortisol ratio as a less invasive cytochrome P450 3A phenotyping method"],"prefix":"10.1111","volume":"90","author":[{"given":"Ryohei","family":"Hirano","sequence":"first","affiliation":[{"name":"Laboratory of Clinical Pharmacy and Experimental Therapeutics, School of Pharmacy Tokyo University of Pharmacy and Life Sciences  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akitomo","family":"Yokokawa","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacy and Experimental Therapeutics, School of Pharmacy Tokyo University of Pharmacy and Life Sciences  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomomi","family":"Furihata","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacy and Experimental Therapeutics, School of Pharmacy Tokyo University of Pharmacy and Life Sciences  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9062-7370","authenticated-orcid":false,"given":"Hiromi","family":"Shibasaki","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacy and Experimental Therapeutics, School of Pharmacy Tokyo University of Pharmacy and Life Sciences  Tokyo 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