RT Journal Article SR Electronic T1 Intraindividual and Interindividual Variabilities in Endogenous Cortisol 6β-Hydroxylation Clearance as an Index for In Vivo CYP3A Phenotyping in Humans JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 475 OP 479 DO 10.1124/dmd.112.048561 VO 41 IS 2 A1 Hiromi Shibasaki A1 Kaori Hosoda A1 Mari Goto A1 Atsushi Suzuki A1 Akitomo Yokokawa A1 Kazuo Ishii A1 Takashi Furuta YR 2013 UL http://dmd.aspetjournals.org/content/41/2/475.abstract AB This study was designed to evaluate the in vivo activity of cytochrome P450 3A (CYP3A) in 49 healthy Japanese subjects aged 22–58 years using endogenous cortisol 6β-hydroxylation clearance [CLm(6β)], a novel biomarker for CYP3A phenotyping. CLm(6β) in the 49 healthy subjects was 2.40 ± 0.79 ml/min with an approximately 4-fold interindividual variability of CYP3A activity. The mean clearance in the 24 women was 2.50 ± 0.89 ml/min; the value in the women was higher than in the 25 men (2.30 ± 0.69 ml/min) by approximately 9%. We also measured the change of CLm(6β) in 14 healthy subjects in the morning at 10:00–12:00 every 2 or 3 days over a period of 36–53 days and observed a 1.5-fold to 3.4-fold day-to-day intraindividual variability in the CYP3A activity. The mean value for CLm(6β) in each subject for 36–53 days was 2.54 ± 0.76 ml/min (n = 14). We also evaluated the CLm(6β) every 2 hours from 8:00–20:00 in 26 healthy subjects. The within-day intraindividual clearance variability was 1.1-fold to 2.5-fold (2.45 ± 0.91 ml/min, n = 26). No characteristic diurnal rhythms were observed in the in vivo activity of CYP3A.