Disease relevance of MLS000028854

• Urinary 6beta-hydroxycortisol (6betaOHF) excretion was measured and compared with free cortisol and 17-hydroxycorticosteroid (17OH) excretion in normal children, patients with Cushing's syndrome or disease (CSD), and patients during cortisol therapy [1].
• Secretion of 6beta-hydroxycortisol by normal human adrenals and adrenocortical adenomas [2].
• Increases in metabolism of valproate and excretion of 6beta-hydroxycortisol in patients with traumatic brain injury [3].
• Microsomal enzyme induction and clinical aggravation of porphyria: the evaluation of human urinary 6beta-hydroxycortisol/cortisol ratio as the index of hepatic CYP3A4 activity [4].
• CONCLUSIONS: Brain trauma results in induction of multiple pathways of valproate metabolism and increases in the 6beta-hydroxycortisol to cortisol ratio, suggesting a non-specific enzyme induction in response to head injury [3].

High impact information on MLS000028854

• In parallel, urinary 6beta-hydroxycortisol, a validated marker of CYP3A induction, was determined [5].
• UDCA did not affect biotransformation of budesonide and urinary excretion of 6beta-hydroxycortisol either in patients or in healthy volunteers [5].
• AIMS: The aim of this study was to evaluate the effect of rifampicin co-administration on the pharmacokinetics of ruboxistaurin and its active metabolite, N-desmethyl ruboxistaurin and, in addition, to compare the changes in pharmacokinetics of ruboxistaurin and N-desmethyl ruboxistaurin with the urinary 6beta-hydroxycortisol : cortisol ratio [6].
• Urinary markers of adrenarche, especially dehydroepiandrosterone and its direct metabolites were elevated in patients, as were urinary 6beta-hydroxycortisol, UFE, and 11beta-HSD2 activity [7].
• The urinary ratio of 6beta-hydroxycortisol to cortisol, which reflects CYP3A4 activity, also increased after dosing with SJW (ratio; 2.1 (95%CI 0.85-3.4)) [8].

Chemical compound and disease context of MLS000028854

• Whether the elevated urinary 6beta-hydroxycortisol and cortisone excretion, observed in the patients, are also present in other forms of hypercortisolism and may thus serve as non-invasive clinical stress markers deserves further study [7].
• Subjects received dapsone 100 mg p.o. followed by an 8-h urine collection for dapsone, dapsone N-hydroxylamine, cortisol, and 6beta-hydroxycortisol concentrations before HIV protease inhibitor administration, and 3 4 weeks into receiving HIV protease inhibitors [9].

Biological context of MLS000028854

• These results show that a CYP3A genetic polymorphism in Japanese persons, based on 6beta-hydroxycortisol excretions, likely does not exist, but there appears to be a broad unimodal distribution of enzyme activity in the population [10].
• The AUC remained unaffected in 1 subject (although 6beta-hydroxycortisol indicated enzyme induction) and decreased in the other 11 subjects [11].

Anatomical context of MLS000028854

• Neither in PMNs nor in lymphocytes, induction of CYP 3A protein expression was observed after rifampicin treatment despite overall induction of CYP 3A activity assessed by the urinary excretion of 6beta-hydroxycortisol [12].

Associations of MLS000028854 with other chemical compounds

• Comparison of urinary 6beta-hydroxycortisol/cortisol ratio between neonates and their mothers [13].
• The 24-hr urinary recoveries of 6beta-hydroxycortisol were reduced by an average of 27% during nelfinavir treatment, consistent with CYP3A inhibition by nelfinavir [14].
• Known inducers of CYP3A, such as rifampin, phenytoin, carbamazepine, and phenobarbital, increase the urinary excretion of 6beta-hydroxycortisol and the ratio of 6beta-hydroxycortisol to cortisol [15].
• Lamotrigine appears to be a weak inducer of UGTs, whereas induction of CYP3A4 seems improbable as the compound does not change the concentrations of oral contraceptives or the urinary excretion of 6beta-hydroxycortisol [16].
• Twenty-six healthy subjects were studied to evaluate their baseline activity of CYP1A2 and XO by the respective urinary metabolic ratios of an 8-h urine sample after an oral 150-mg dose of caffeine and of CYP3A by a urinary excretion ratio of 6beta-hydroxycortisol (6beta-HC) to free cortisol (FC) [17].

Gene context of MLS000028854

• When compared with healthy Chinese population data, the 6beta-hydroxycortisol to free cortisol ratio data suggested that these alleles (CYP3A4*4, CYP3A4*5, and CYP3A4*6) may decrease the CYP3A4 activity [18].
• Increase in urinary excretion of 6beta-hydroxycortisol in common marmosets as a marker of hepatic CYP3A induction [19].
• Cytochrome P4503A4 (CYP3A4) inducibility was measured by comparing the urinary metabolic ratio of 6beta-hydroxycortisol/cortisol on day 14 and 19, Lymphocyte P-gp expression and activity was not induced by rifampicin, while it increased CYP3A4 activity from 5.0 +/- 4.0 to 22.9 +/- 16.6 (P < 0.001) [20].
• Liquid chromatographic determination of urinary 6beta-hydroxycortisol to assess cytochrome p-450 3A activity in HIV positive pregnant women [21].
• RESULTS: Urine excretion of 6beta-hydroxycortisol was significantly elevated during treatment with rifampin compared with prestudy, indicating enzyme induction [11].

Analytical, diagnostic and therapeutic context of MLS000028854

• Radioimmunoassay of 6beta-hydroxycortisol in human plasma and urine [22].
• In the process of clinical study, it was found that urinary excretion ratios for 6beta-hydroxycortisol and free cortisol increased significantly in parallel with decreases in the plasma concentrations of MKC-963 after repeated oral administration of the compound to healthy volunteers [23].
• Cortisol and 6beta-hydroxycortisol were quantified using high-performance liquid chromatography with ultraviolet detection [24].
• Quantitative determination by HPLC of urinary 6beta-hydroxycortisol, an indicator of enzyme induction by rifampicin and antiepileptic drugs [25].
• METHODS: In this open-label, single-sequence, crossover study, 12 healthy subjects received a single oral 4-mg dose of everolimus alone and again after an 8-day pretreatment with rifampin 600 mg/d. Urinary excretion of 6beta-hydroxycortisol was measured at various time points during rifampin treatment as a marker of CYP3A4 induction [11].

References