Quantification of cortisol and 6 beta-hydroxycortisol in human urine by LC-MS/MS, and gender-specific evaluation of the metabolic ratio as biomarker of CYP3A activity

Lutz, Ursula; Bittner, Nataly; Ufer, Mike; Lutz, Werner

doi:10.1016/j.jchromb.2009.11.023

Cited by 39 publications

(26 citation statements)

References 24 publications

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“…We found normal levels of 6b-hydroxycortisol (39) on standard treatment, which indicate that its contribution to the metabolism of cortisol is minor. However, large interindividual differences in CYP3A4 activity have been reported (39). In contrast to others, we did not find evidence of GFJ inhibition of CYP3A4; the 6b-hydroxycortisol/cortisol ratio was unchanged.…”

Section: Discussioncontrasting

confidence: 99%

Grapefruit juice and licorice increase cortisol availability in patients with Addison's disease

Methlie

Husebye

Hustad

et al. 2011

European Journal of Endocrinology

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Objective: Failure to mirror the diurnal cortisol profile could contribute to the impaired subjective health status in Addison's disease (AD). Some patients report benefit from the use of various nutritional compounds. The objective of this study was to investigate the impact of licorice and grapefruit juice (GFJ) on the absorption and metabolism of cortisone acetate (CA). Design: Patients (nZ17) with AD on stable CA replacement therapy were recruited from the outpatient clinic at Haukeland University Hospital, Norway. They were assessed on their ordinary CA medication and following two 3-day periods of co-administration of licorice or GFJ. Methods: Time series of glucocorticoids (GCs) in serum and saliva were obtained, and GCs in 24 h urine samples were determined. The main outcome measure was the area under the curve (AUC) for serum cortisol in the first 2.6 h after orally administered CA. Results: Compared with the ordinary treatment, the median AUC for serum cortisol increased with licorice (53 783 vs 50 882, P!0.05) and GFJ (60 661 vs 50 882, P!0.05). Median cortisol levels in serum were also elevated 2.6 h after tablet ingestion (licorice 223 vs 186 nmol/l, P!0.05; GFJ 337 vs 186 nmol/l, P!0.01). Licorice increased the median urinary cortisol/cortisone ratio (0.43 vs 0.21, P!0.00001), whereas GFJ increased the (allo-tetrahydrocortisolCtetrahydrocortisol)/tetrahydrocortisone ratio (0.55 vs 0.43, P!0.05).

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Section: Discussioncontrasting

confidence: 99%

Grapefruit juice and licorice increase cortisol availability in patients with Addison's disease

Methlie

Husebye

Hustad

et al. 2011

European Journal of Endocrinology

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“…1), which is consistent with previous studies using CYP3A substrates or markers (Horsmans et al, 1992;Harris et al, 1995;Inagaki et al, 2002;Zhu et al, 2003;Cotreau et al, 2005;Lutz et al, 2010); however, we found no statistically significant sex-related difference (P = 0.37). The presence of the female sex steroids estrogen and progesterone in vivo may play a role in the modulation of this sex-related difference.…”

Section: Discussionsupporting

confidence: 92%

Intraindividual and Interindividual Variabilities in Endogenous Cortisol 6β-Hydroxylation Clearance as an Index for In Vivo CYP3A Phenotyping in Humans

et al. 2012

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This 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 6b-hydroxylation clearance [CLm(6b)], a novel biomarker for CYP3A phenotyping. CLm(6b) in the 49 healthy subjects was 2.40 6 0.79 ml/min with an approximately 4-fold interindividual variability of CYP3A activity. The mean clearance in the 24 women was 2.50 6 0.89 ml/min; the value in the women was higher than in the 25 men (2.30 6 0.69 ml/min) by approximately 9%. We also measured the change of CLm(6b) in 14 healthy subjects in the morning at 10:00-12:00 every 2 or 3 days over a period of 36-53 days and observed a 1.5-fold to 3.4-fold dayto-day intraindividual variability in the CYP3A activity. The mean value for CLm(6b) in each subject for 36-53 days was 2.54 6 0.76 ml/min (n = 14). We also evaluated the CLm(6b) every 2 hours from 8:00-20:00 in 26 healthy subjects. The within-day intraindividual clearance variability was 1.1-fold to 2.5-fold (2.45 6 0.91 ml/min, n = 26). No characteristic diurnal rhythms were observed in the in vivo activity of CYP3A.

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“…Measurement of plasma levels of inflammatory cytokines, such as IL-6, might be useful in some cases but is complicated by the pleiotropic nature of cytokine action. A more direct measurement of CYP activity is preferred, and there is progress in the development of endogenous markers of CYP metabolism (Lutz, Bittner, Ufer, & Lutz, 2010;Shin et al, 2013). This strategy avoids the need to administer probe substrates that might have unpredictable effects on physiology.…”

Section: Clinical Studiesmentioning

confidence: 99%

Role of Cytochrome P450s in Inflammation

Christmas

2015

Advances in Pharmacology

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Quantification of cortisol and 6 beta-hydroxycortisol in human urine by LC-MS/MS, and gender-specific evaluation of the metabolic ratio as biomarker of CYP3A activity

Cited by 39 publications

References 24 publications

Grapefruit juice and licorice increase cortisol availability in patients with Addison's disease

Grapefruit juice and licorice increase cortisol availability in patients with Addison's disease

Intraindividual and Interindividual Variabilities in Endogenous Cortisol 6β-Hydroxylation Clearance as an Index for In Vivo CYP3A Phenotyping in Humans

Role of Cytochrome P450s in Inflammation

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