Urinary 6#beta#-hydroxycortisol/cortisol ratio does not reflect in vivo CYP3A activity in humans

摘要

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