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

Eur J Clin Pharmacol. 1989;36(1):39-46. doi: 10.1007/BF00561021.

Abstract

The effect of enzyme induction by antipyrine, phenobarbitone and rifampicin on the time-course of urinary 6 beta-hydroxycortisol (6 beta-OHC) excretion was investigated in healthy volunteers. The drugs were given chronically for either seven or 14 days. Significant increases in 6 beta-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) 6 beta-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 6 beta-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 6 beta-hydroxylation has been fully characterized.

MeSH terms

  • Adult
  • Antipyrine / administration & dosage
  • Antipyrine / pharmacokinetics
  • Antipyrine / pharmacology*
  • Enzyme Induction / drug effects
  • Female
  • Humans
  • Hydrocortisone / analogs & derivatives*
  • Hydrocortisone / urine
  • Kinetics
  • Liver / enzymology
  • Male
  • Mixed Function Oxygenases / biosynthesis*
  • Phenobarbital / administration & dosage
  • Phenobarbital / pharmacology*
  • Rifampin / administration & dosage
  • Rifampin / pharmacology*
  • Time Factors

Substances

  • 6 beta-hydroxycortisol
  • Mixed Function Oxygenases
  • Antipyrine
  • Rifampin
  • Hydrocortisone
  • Phenobarbital