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Interindividual and Intraindividual Variability of the Urinary 6β‐Hydroxycortisol/Cortisol Ratio in Chinese Subjects: Implications of Its Use for Evaluating CYP3A Activity
Author(s) -
Yin Ophelia Q. P.,
Shi Xiaojin,
Tomlinson Brian,
Chow Moses S. S.
Publication year - 2004
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270004269760
Subject(s) - morning , confidence interval , medicine , urinary system , cyp3a , endocrinology , urine , analysis of variance , population , hydrocortisone , cortisol awakening response , physiology , metabolism , environmental health , cytochrome p450
The present study determined the interindividual and intrandividual variability of the urinary 6β‐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 6β‐hydroxycortisol. There were no significant differences in the mean 6β‐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 6β‐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 6β‐hydroxycortisol/cortisol ratio was estimated to be 0.91. The genetic component is likely to contribute significantly to the variability of the 6β‐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.