{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T11:37:38Z","timestamp":1792237058877,"version":"4.4.0"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,5,2]],"date-time":"2006-05-02T00:00:00Z","timestamp":1146528000000},"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":[[2006,8]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>A non\u2010invasive proposed method for measuring CYP3A activity is the urinary 6\u03b2\u2010hydroxycortisol:cortisol ratio. This ratio has been used as an indicator of CYP3A induction and inhibition, with mixed results. This investigation evaluated the relationship between a validated, biomarker, intravenous midazolam clearance and the urinary cortisol ratio under constitutive conditions and with the influence of a moderate CYP3A inhibitor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a sequential, cross\u2010over study design. Intravenous midazolam 0.025\u2003mg kg<jats:sup>\u22121<\/jats:sup> was administered to 10 male and 10 female subjects once every 14\u2003days for 4\u2003months. Fluvoxamine 150\u2003mg\u2003day<jats:sup>\u22121<\/jats:sup> was given to all subjects during the last two visits. Total body clearance of midazolam and urinary 6\u03b2\u2010hydroxycortisol:cortisol molar ratio were used as biomarkers of hepatic CYP3A activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>No significant correlations were found between these two markers (<jats:italic>r<\/jats:italic><jats:sup>2<\/jats:sup>\u2003&lt;\u20030.5, <jats:italic>P<\/jats:italic>\u2003&gt;\u20030.05). Larger interindividual and intra\u2010individual variability in CYP3A activity was observed in 6\u03b2\u2010hydroxycortisol:cortisol ratios compared with midazolam clearances. With fluvoxamine therapy, midazolam clearance values decreased approximately 1.5\u2010fold and cortisol ratios decreased approximately 1.9\u2010fold.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The high intra\u2010individual variability of the urinary cortisol ratio, compared with midazolam, makes this a suboptimal CYP3A phenotyping tool.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1365-2125.2006.02628.x","type":"journal-article","created":{"date-parts":[[2006,5,2]],"date-time":"2006-05-02T18:07:52Z","timestamp":1146593272000},"page":"187-195","source":"Crossref","is-referenced-by-count":44,"title":["Poor correlation between 6\u03b2\u2010hydroxycortisol:cortisol molar ratios and midazolam clearance as measure of hepatic CYP3A activity"],"prefix":"10.1111","volume":"62","author":[{"given":"Ya\u2010Chi","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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