Interindividual variability of coumarin 7-hydroxylation in healthy volunteers

Pharmacogenetics. 1992 Oct;2(5):227-33. doi: 10.1097/00008571-199210000-00005.

Abstract

A test designed to estimate the extent and rate of formation of 7-hydroxycoumarin by measuring the urinary excretion of the metabolite in humans after administering 5 mg coumarin was developed. Coumarin was rapidly metabolized after oral administration and more than 95% of the 7OHC formed was excreted in 4 h. The total amount of 7OHC formed was 64 +/- 15% (mean +/- SD, variation 20-100%) of the dose given. The percentage of 7OHC excreted in 2 h, as compared with the 7OHC excretion in 4 h, was found to be a constant and stable individual characteristic for the rate of the formation of 7OHC ('2 h coumarin test'). In 110 volunteers, there was a great interindividual variability in the extent and rate of 7OHC formation. Four individuals had relatively 'slow' coumarin test values (50-60%), but much larger populations would be needed for the demonstration of polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aryl Hydrocarbon Hydroxylases*
  • Coumarins / metabolism*
  • Cytochrome P-450 CYP2A6
  • Cytochrome P-450 Enzyme System / genetics*
  • Cytochrome P-450 Enzyme System / metabolism*
  • Female
  • Genetic Variation
  • Humans
  • Hydroxylation
  • Kinetics
  • Male
  • Middle Aged
  • Mixed Function Oxygenases / genetics*
  • Mixed Function Oxygenases / metabolism*
  • Reference Values
  • Reproducibility of Results
  • Umbelliferones / biosynthesis
  • Umbelliferones / urine

Substances

  • Coumarins
  • Umbelliferones
  • 7-hydroxycoumarin
  • Cytochrome P-450 Enzyme System
  • coumarin
  • Mixed Function Oxygenases
  • Aryl Hydrocarbon Hydroxylases
  • Cytochrome P-450 CYP2A6