Abstract
The present 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, a novel biomarker for CYP3A-phenotyping. The 6β-hydroxylation clearances (CLm(6β)) in 49 healthy subjects were 2.40 ± 0.79 ml/min with an approximately 4-fold inter-individual variability of CYP3A activity. The mean clearance in 24 female subjects was 2.50 ± 0.89 ml/min, and the value was higher than that in 25 male subjects (2.30 ± 0.69 ml/min) by approximately 9%. Furthermore, changes of the 6β-hydroxylation clearances (CLm(6β)) in 14 healthy subjects were followed once at 10:00-12:00 in the morning at least every 2 or 3 days over a period of 36 - 53 days, indicating 1.5 ~ 3.4-fold day-to-day intra-individual variability of 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 6β-hydroxylation clearances (CLm(6β)) every 2 hours from 8:00 to 20:00 in 26 healthy subjects. Within-day intra-individual variability of the clearance was 1.1 ~ 2.5-fold (2.45 ± 0.91 ml/min, n = 26) and no characteristic diurnal rhythms were observed in the in vivo activity of CYP3A.
- Received September 5, 2012.
- Accepted November 21, 2012.
- The American Society for Pharmacology and Experimental Therapeutics