Interindividual and intraindividual variability of the urinary 6beta-Hydroxycortisol/Cortisol ratio in Chinese subjects: implications of its use for evaluating CYP3A activity.
The present study determined the interindividual and intrandividual variability of the urinary 6beta-hydroxycortisol/cortisol ratio, a useful marker for CYP3A induction and inhibition in Chinese subjects. The study consisted of 2 parts. In part I, 82 healthy male Chinese subjects underwent 3 study sessions, each separated by a 1-week interval. In part II, 20 subjects who initially completed part I underwent another 3 sessions over a period of 3 to 4 months. During each session, a first-morning urine specimen was collected from each subject for the quantification of urinary concentrations of cortisol and 6beta-hydroxycortisol. There were no significant differences in the mean 6beta-hydroxycortisol/cortisol ratios among the 3 sessions (P > .05, 1-way analysis of variance) for both part I and part II of the study. A normal distribution of the 6beta-hydroxycortisol/cortisol ratio was observed (P = .849, Kolmogorov-Smirnov test). This ratio varied 30-fold (range, 0.76-23.23) among the study subjects. The mean intraindividual variabilities during the short (3-week) and long (3- to 4-month) periods were 30.9% +/- 17.5% and 32.2% +/- 17.1%, respectively. The genetic fraction contributing to the observed variability in the 6beta-hydroxycortisol/cortisol ratio was estimated to be 0.91. The genetic component is likely to contribute significantly to the variability of the 6beta-hydroxycortisol/cortisol ratio, and such variability should be considered when the ratio is used to evaluate CYP3A induction or inhibition in a given ethnic population.
Yin
Ophelia Q P
OQ
School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
Shi
Xiaojin
X
Tomlinson
Brian
B
Chow
Moses S S
MS
D000328:Adult; D000704:Analysis of Variance; D044466:Asian People; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D005838:Genotype; D006723:Hong Kong / Q000208:ethnology; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000652:urine*; D008297:Male; D013045:Species Specificity
C001380:6 beta-hydroxycortisol; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; D006854:Hydrocortisone