Grapefruit juice inhibits 7-hydroxylation of coumarin in healthy volunteers.
The effect of grapefruit juice on the urinary excretion of 7-hydroxycoumarin after oral administration of 10 mg coumarin, as an index of cytochrome P450 dependent coumarin metabolism, has been investigated in an open, randomised cross over study in 13 healthy volunteers (7 female, 6 male). The percentage of 7-hydroxycoumarin found in urine was significantly decreased up to 8 h after simultaneous intake of 300 ml grapefruit juice. If the same volume of juice was swallowed 30 min prior to the administration of coumarin, 7-hydroxycoumarin excretion was delayed by up to 6 h. MRTexcr. of coumarin was 70% extended by coadministration of grapefruit juice. It appears that grapefruit flavonoids inhibit cytochrome P450 2A dependent metabolic pathways. The mechanism of cytochrome P450 inhibition by these flavonoids is still poorly understood.
Merkel
U
U
Institute of Clinical Pharmacology, University of Jena, Germany.
Sigusch
H
H
Hoffmann
A
A
D000328:Adult; D000704:Analysis of Variance; D001628:Beverages; D002957:Citrus; D003374:Coumarins / Q000378:metabolism* / Q000652:urine; D005260:Female; D006801:Humans; D006900:Hydroxylation; D008297:Male; D012016:Reference Values
D003374:Coumarins; C030123:coumarin