Absence of CYP3A genetic polymorphism assessed by urinary excretion of 6 beta-hydroxycortisol in 102 healthy subjects on rifampicin

Pharmacol Toxicol. 1992 Oct;71(4):258-61. doi: 10.1111/j.1600-0773.1992.tb00980.x.

Abstract

A previous study has demonstrated that the urinary level of 6 beta-hydroxycortisol is a marker of liver CYP3A content after induction by rifampicin. To put in evidence an eventual genetic polymorphism for this cytochrome, the frequency distribution of 6 beta-hydroxycortisol excretion was investigated in 102 healthy Caucasians before and after 6 days of oral rifampicin administration (600 mg daily). After rifampicin treatment, a wide interindividual distribution was observed but no clear bimodality. Moreover the mean 6 beta-hydroxycortisol level was higher in women (n = 38) than in men (n = 64). These observations do not favour the existence of a CYP3A genetic polymorphism based on 6 beta-hydroxycortisol excretion but evoke a sexual dimorphism. However, CYP3A is composed of at least four enzymes and as the enzyme(s) responsible for cortisol 6 beta-hydroxylation is (are) not perfectly known, it can not be excluded that a genetic polymorphism does exist for one enzyme of this family.

MeSH terms

  • 17-Hydroxycorticosteroids / urine
  • Administration, Oral
  • Adult
  • Aryl Hydrocarbon Hydroxylases*
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / genetics*
  • Female
  • Humans
  • Hydrocortisone / analogs & derivatives*
  • Hydrocortisone / urine
  • Male
  • Oxidoreductases, N-Demethylating / genetics*
  • Polymorphism, Genetic / genetics*
  • Rifampin / pharmacology*

Substances

  • 17-Hydroxycorticosteroids
  • 6 beta-hydroxycortisol
  • Cytochrome P-450 Enzyme System
  • Aryl Hydrocarbon Hydroxylases
  • Cytochrome P-450 CYP3A
  • Oxidoreductases, N-Demethylating
  • Rifampin
  • Hydrocortisone