Interindividual variability of coumarin 7-hydroxylation in healthy volunteers.
Rautio, Arja 1; Kraul, Holger 1,2; Kojo, Anneli 3; Salmela, Erja 1; Pelkonen, Olavi 1
[Article] Pharmacogenetics. 2(5):227-233, October 1992.

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A test designed to estimate the extent and rate of formation of 7-hydroxycoumarin[P] 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 4h. The total amount of 7OHC formed was 64 /-5% (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.

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