Abstract
A rationale is described to explain that the urinary 6β-hydroxycortisol/cortisol (6β-OHF/F) ratio does not appropriately reflect in vivo CYP3A activity (phenotype). To evaluate CYP3A-mediated 6β-hydroxylation of cortisol in vivo, “fractional metabolic clearance” specific for the 6β-hydroxylation was calculated by measuring both urinary 6β-hydroxycortisol and plasma cortisol after administering stable isotopically labelled cortisol to humans. It is shown that the urinary 6β-OHF/F ratio is a function of metabolic clearance and renal clearance of cortisol. The observed intra- and interindividual variabilities of the renal clearance indicate that the urinary ratio is not appropriate for the CYP3A phenotyping. We propose a safe and reliable CYP3A-phenotyping.
