The ratio of urinary 6-beta-hydroxycortisol to urinary cortisol can serve as a phenotypic marker of CYP3A4 activity. An increase in the ratio from baseline indicates enzyme induction, while a decrease indicates enzyme inhibition.
Analytic method: liquid chromatography mass spectroscopy (LC-MS)
Biochemistry: Cortisol is metabolized to 6-beta-hydroxycortisol by CYP3A4 activity.
Specimen collection: 24 hour urine collection kept refrigerated, with an aliquot sent frozen to the laboratory for analysis.
molecular weight of cortisol (compound F): 362.47 grams
molecular weight of 6-beta-hydroxycortisol: 378.46 (cortisol plus OH)
ratio =
= (24 hour urine 6-beta-hydroxycortisol in mmol) / (24 hour urine cortisol in mmol)
Interpretation:
• The mean ratio is 6.
• A significant increase (> 30%) in the ratio indicates enzyme induction.
• A significant decrease in the ratio indicates enzyme inhibition.
Limitations:
• The test is unreliable in a patient with a liver transplant.
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