Within-person variability of urinary 6beta-hydroxycortisol to urinaryl ratios in Caucasian women.

Steroids

Department of Medicine and Vanderbilt-Ingram Cancer Centre, Vanderbilt University, Nashville, IN 37232-8300, USA.

Published: January 2004

Cortisol is metabolized to 6beta-hydroxycortisol by human cytochrome p450-3A4 (CYP3A4), an important enzyme involved in the metabolism of a variety of exogenous and endogenous compounds. Both cortisol and 6beta-hydroxycortisol are excreted in urine, and the ratio of these steroids has been proposed as an indicator of CYP3A4 activity. We evaluated within-person variability of this biomarker in 10 healthy Caucasian women, aged 23-58 years. Each study participant was asked to provide a fasting morning urine sample once a week consecutively for 8 weeks. Urinary cortisol and 6beta-hydroxycortisol were determined by immunoassay kits purchased from the DiaSorin (Stillwater, MN) and the Stabiligen (Nancy, France), respectively. The coefficients of variation (CV) of urinary 6beta-hydroxycortisol to cortisol ratios from study participants ranged from 16.7 to 51.4% (mean, 31.1%) over the study period. The level of the ratio measured in any single urine sample was correlated reasonably well with the average of the ratios over the 8-week study period from the same woman, with the mean correlation coefficient of 0.79. These results indicated that urinary 6beta-hydroxycortisol to cortisol ratios measured in a spot urine sample may reflect the level of this biomarker over a relatively longer time period in Caucasian women, and thus, it can be used in epidemiologic studies as a biomarker to evaluate the association between CYP3A4 activity and disease risk.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.steroids.2003.10.004DOI Listing

Publication Analysis

Top Keywords

urinary 6beta-hydroxycortisol
12
caucasian women
12
urine sample
12
within-person variability
8
cortisol 6beta-hydroxycortisol
8
cyp3a4 activity
8
6beta-hydroxycortisol cortisol
8
cortisol ratios
8
study period
8
6beta-hydroxycortisol
6

Similar Publications

This study evaluates the impact of acute pyelonephritis in pregnant women on the in vivo activity of renal OAT3 using the endogenous biomarker (EB) 6β-hydroxycortisol (6β-OHF) renal clearance (CL 6β-OHF) and AUC validated by correlating with the secretion clearance (CL) of the probe drug furosemide. Additionally, 6β-OHF formation clearance (CL 6β-OHF) as well as urinary (Ae/Ae) and plasma (AUC/AUC) ratios were also evaluated as EB for hepatic CYP3A activity. Pregnant women in their third trimester of gestation, diagnosed with acute pyelonephritis, were recruited before (pre-treatment, n = 8) and after (post-treatment, n = 8) cefuroxime treatment and resolution of acute pyelonephritis.

View Article and Find Full Text PDF

Lenvatinib (LEN), a multitarget tyrosine kinase inhibitor used in various cancer treatments, is mainly metabolized by cytochrome P450 3A (CYP3A) enzymes. The importance of therapeutic drug monitoring (TDM) in patients administered LEN has been proposed. Although some biomarkers of endogenous CYP3A activity have been reported, their utility in dosage adjustments has not been well evaluated.

View Article and Find Full Text PDF

CYP3A4, which contributes to the metabolism of more than 30% of clinically used drugs, exhibits high variation in its activity; therefore, predicting CYP3A4 activity before drug treatment is vital for determining the optimal dosage for each patient. We aimed to develop and validate an LC-tandem mass spectrometry (LC-MS/MS) method that simultaneously measures the levels of CYP3A4 activity-related predictive biomarkers (6β-hydroxycortisol (6β-OHC), cortisol (C), 1β-hydroxydeoxycholic acid (1β-OHDCA), and deoxycholic acid (DCA)). Chromatographic separation was achieved using a YMC-Triart C18 column and a gradient flow of the mobile phase comprising deionized water/25% ammonia solution (100 : 0.

View Article and Find Full Text PDF

The objective of the current research was to develop a liquid chromatography-MS (LC-MS) methodology for the determination of free cortisol and its 15 endogenous metabolites (6β-hydroxycortisol, 20α-dihydrocortisol, 20α-dihydrocortisone, 20-β-dihydrocortisol, 20β-dihydrocortisone, prednisolone, cortisone, α-cortolone, β-cortolone, allotetrahydrocortisol, 5α-dihydrocortisol, tetrahydrocortisol, allotetrahydrocortisone, 5β-dihydrocortisol, tetrahydrocortisone) in human urine. Due to its optimal performance, a linear ion trap operating in ESI negative ion mode was chosen for the spectrometric analysis, performing MS and MS experiments. The method was validated for limit of detection (LOD) and limit of quantification (LOQ) (0.

View Article and Find Full Text PDF

Spontaneous hypercortisolism (HC) is a common endocrine disease of senior dogs, often overlapping in selected clinical signs and hematologic and blood biochemical abnormalities with nonadrenal diseases (NADs). HC and NAD could differentially affect cortisol metabolism, which is a complex 10-enzymatic pathway process. HC might also affect blood and urine lactate levels through its effects on mitochondrial function.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!