title: Interindividual variability of coumarin 7-hydroxylation in healthy volunteers.
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.
authors.affiliation: Department of Pharmacology and Toxicology, University of Oulu, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Rautio
authors.forename: H
authors.initials: H
authors.lastname: Kraul
authors.forename: A
authors.initials: A
authors.lastname: Kojo
authors.forename: E
authors.initials: E
authors.lastname: Salmela
authors.forename: O
authors.initials: O
authors.lastname: Pelkonen
mesh_terms: D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases; D003374:Coumarins / Q000378:metabolism*; D065637:Cytochrome P-450 CYP2A6; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D006900:Hydroxylation; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism*; D012016:Reference Values; D015203:Reproducibility of Results; D014468:Umbelliferones / Q000096:biosynthesis / Q000652:urine
chemical_list: D003374:Coumarins; D014468:Umbelliferones; C031477:7-hydroxycoumarin; D003577:Cytochrome P-450 Enzyme System; C030123:coumarin; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; D065637:Cytochrome P-450 CYP2A6