Circadian variation of the urinary 6β-hydroxycortisol to cortisol ratio that would reflect hepatic CYP3A activity

Ohno, Munekazu; Yamaguchi, Ikumi; Ito, Toshifumi; Saiki, Kayoko; Yamamoto, Ichiro; Azuma, Junichi

doi:10.1007/s002280050708

Cited by 71 publications

(50 citation statements)

References 19 publications

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“…The urine F concentration decreased during the afternoon and the urinary 6b-OHF/F ratio exhibited significant diurnal variation with a peak between 1,300 and 2,100 (Table 3). These results are in good agreement with previous reports [12,13]. It was suggested that the diurnal variation of the urinary 6b-OHF/F ratio may infer the circadian rhythm of hepatic CYP3A activity [12] although it may just reflect the variation in the availability of the substrate F.…”

Section: Clinical Applicationsupporting

confidence: 91%

Simultaneous Determination of Cortisol, Cortisone, and 6β-Hydroxycortisol in Human Urine by UPLC with UV Detector and Application to Determine Diurnal Variations

Xiao

Chan

et al. 2011

Chromatographia

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In the present studies, a simple rapid ultra performance liquid chromatography (UPLC) method with UV detection for the simultaneous determination of cortisol, cortisone and 6b-hydroxycortisol in human urine was developed. The three analytes and the internal standard dexamethasone were separated on a Waters Acquity UPLC-Tunable UV system with an Acquity UPLC BEH C18 column (50 9 2.1 mm ID, 1.7 lm) using a gradient elution of methanol and water (containing 0.01% formic acid) with a run time of 7 min. The method was accurate and precise, over the ranges of 5-200 ng mL -1 for cortisol, and 10-1,000 ng mL -1 for both cortisone and 6b-hydroxycortisol, and showed good linearity (r 2 [ 0.999). This method was applied for the measurement of cortisol, cortisone and 6b-hydroxycortisol in samples collected over different periods as a tool to assess the activity of CYP3A and 11b-hydroxysteroid dehydrogenase type 2 enzymes.

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Section: Clinical Applicationsupporting

confidence: 91%

Simultaneous Determination of Cortisol, Cortisone, and 6β-Hydroxycortisol in Human Urine by UPLC with UV Detector and Application to Determine Diurnal Variations

Xiao

Chan

et al. 2011

Chromatographia

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“…Some results have shown the absence of any changes in the ratio of 6b-OHF/F in spot urine throughout the day (Galteau and Shamsa, 2003;Micuda et al, 2007). Conversely one report indicated a diurnal rhythm, with increased levels in the evening (Ohno et al, 2000). It should be noted that the urinary ratio 6b-OHF/F is valid as the index for in vivo CYP3A activity only when the renal clearance of cortisol is consistent (Furuta et al, 2001(Furuta et al, , 2003Peng et al, 2011), because the urinary ratio 6b-OHF/F is a function of two independent parameters: metabolic clearance specific for 6b-hydroxylation and renal clearance of cortisol.…”

Section: Discussionmentioning

confidence: 99%

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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“…Some endogenous markers have been in use for decades, such as the urinary 6b-hydroxycortisol/cortisol metabolic ratio (reviewed in Galteau and Shamsa, 2003), whereas others such as 4b-hydroxycholesterol or 4b,25-dihydroxyvitamin D 3 were identified more recently (Bodin et al, 2001;Wang et al, 2012). Because the formation and subsequent excretion of cortisol follows a diurnal pattern, the 6b-hydroxycortisol/ cortisol ratio determined over a long urine collection interval (e.g., 24 hours) is typically reported, rather than the concentration of metabolite alone (Ohno et al, 2000;Hu et al, 2009;Luo et al, 2009). Despite numerous studies with urinary 6b-hydroxycortisol, several reports demonstrate a lack of correlation with CYP3A substrates, especially under basal conditions (Chen et al, 2006;Luo et al, 2009;Dutreix et al, 2014).…”

Section: Interindividual Variability In Cyp2d6-mediated Drugmentioning

confidence: 99%

Interindividual Variability in Cytochrome P450-Mediated Drug Metabolism

Tracy¹,

Chaudhry²,

Prasad³

et al. 2015

Drug Metabolism and Disposition

151

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The cytochrome P450 (P450) enzymes are the predominant enzyme system involved in human drug metabolism. Alterations in the expression and/or activity of these enzymes result in changes in pharmacokinetics (and consequently the pharmacodynamics) of drugs that are metabolized by this set of enzymes. Apart from changes in activity as a result of drug-drug interactions (by P450 induction or inhibition), the P450 enzymes can exhibit substantial interindividual variation in basal expression and/or activity, leading to differences in the rates of drug elimination and response. This interindividual variation can result from a myriad of factors, including genetic variation in the promoter or coding regions, variation in transcriptional regulators, alterations in microRNA that affect P450 expression, and ontogenic changes due to exposure to xenobiotics during the developmental and early postnatal periods. Other than administering a probe drug or cocktail of drugs to obtain the phenotype or conducting a genetic analysis to determine genotype, methods to determine interindividual variation are limited. Phenotyping via a probe drug requires exposure to a xenobiotic, and genotyping is not always well correlated with phenotype, making both methodologies less than ideal. This article describes recent work evaluating the effect of some of these factors on interindividual variation in human P450-mediated metabolism and the potential utility of endogenous probe compounds to assess rates of drug metabolism among individuals.

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Circadian variation of the urinary 6β-hydroxycortisol to cortisol ratio that would reflect hepatic CYP3A activity

Cited by 71 publications

References 19 publications

Simultaneous Determination of Cortisol, Cortisone, and 6β-Hydroxycortisol in Human Urine by UPLC with UV Detector and Application to Determine Diurnal Variations

Simultaneous Determination of Cortisol, Cortisone, and 6β-Hydroxycortisol in Human Urine by UPLC with UV Detector and Application to Determine Diurnal Variations

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

Interindividual Variability in Cytochrome P450-Mediated Drug Metabolism

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