Urinary excretion of 6?-hydroxycortisol and the time course measurement of enzyme induction in man

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Abstract
The effect of enzyme induction by antipyrine, phenobarbitone and rifampicin on the time-course of urinary 6β-hydroxycortisol (6β-OHC) excretion was investigated in healthy volunteers. The drugs were given chronically for either seven or 14 days. Significant increases in 6β-OHC excretion were observed after 4 days administration of antipyrine (1.2 g), 13 days administration of phenobarbitone (100 mg), and only 2 days administration of rifampicin (0.6 or 1.2 g). During 14 days rifampicin administration (1.2 g) 6β-OHC excretion, for individual subjects, reached a maximum on Days 11–14 when excretion was significantly greater than on day 7. On stopping rifampicin, in a 7-day study, excretion decreased over the next six days, but still remained significantly elevated compared to the original control values. These studies show that measurement of urinary 6β-hydroxycortisol provides a simple non-invasive method with which to monitor the time-course of enzyme induction by drugs in man. However, the method cannot be used to predict clinically important drug interactions until the cytochrome P-450 enzyme responsible for cortisol 6β-hydroxylation has been fully characterized.