Morning spot and 24-hour urinary 6 beta-hydroxycortisol to cortisol ratios: Intraindividual variability and correlation under basal conditions and conditions of CYP 3A4 induction
Jq. Tran et al., Morning spot and 24-hour urinary 6 beta-hydroxycortisol to cortisol ratios: Intraindividual variability and correlation under basal conditions and conditions of CYP 3A4 induction, J CLIN PHAR, 39(5), 1999, pp. 487-494
A single spot urine collection to measure the ratio of 6 beta-hydroxycortis
ol (6 beta-OHC) to free cortisol (C) has been proposed as a research tool f
or the assessment of CYP3A4 induction. However, intraindividual variability
in 6 beta-OHC/C under basal conditions and conditions of induction has not
been prospectively evaluated, and findings on the correlation between morn
ing spot and 24-hour urinary ratios have been conflicting. In this study, t
he variability in morning spot and 24-hour urinary 6 beta-OHC/C ratios was
assessed in 15 healthy adult male volunteers before, during, and after oral
administration of rifampin 600 mg once daily for 14 days. In addition, the
correlation between morning spot and 24-hour urinary ratios measured under
baseline, maximum induction, and postinduction was determined. Intraindivi
dual coefficients of variation (CVs) at baseline for the morning spot and 2
4-hour ratios were 54.3% and 57.1%, respectively, and were not changed sign
ificantly during induction. No significant differences were detected in the
variability between the morning spot and 24- hour ratios at baseline, maxi
mum induction, or postinduction. A good correlation (r = 0.61, p < 0.0001)
was detected between the mean morning spot and 24-hour urinary ratios. Mean
(+/- SEM) percent increases in the morning spot and 24-hour ratios at maxi
mum induction relative to baseline were 320% +/- 73% and 137% +/- 30%, resp
ectively (p = 0.019). AII 15 subjects had an increase in the mean morning s
pot ratio at maximum induction relative to baseline, whereas 12 subjects sh
owed an increase in the mean 24-hour ratio. The time course of changes in t
he mean morning spot urinary ratio in response to a 14-day course of rifamp
in was also similar to that reported previously in a study using 24-hour ur
ine collections. These findings suggest that measurement of the morning spo
t urinary 6 beta-OHC/C ratio is an effective and efficient method for evalu
ating the potential of investigational agents to induce CYP3A4. (C) 1999 th
e American College of Clinical Pharmacology.