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Active components in grapefruit juice, which modulate a cytochrome P450 (CYP3A) activity, were investigated. CYP3A-catalyzed 6beta-hydroxylation of testosterone in livers of rat and human was inhibited by the addition of an ethyl acetate-extract of grapefruit juice. Several components of grapefruit juice, including naringin, naringenin, limonin and obacunone, also showed inhibitory effects in human liver microsomes. However, the amounts of these components in grapefruit juice are too low to account for the inhibition by the ethyl acetate-extracts. Analyses with HPLC indicate the existence of inhibitory components in the extract, which are distinct from these known compounds and are specific to grapefruit juice. These results suggest that hydrophobic components other than flavonoids, probably coumarin derivatives, are responsible for the inhibitory effect of grapefruit juice.

Grapefruit Component Interacting with Rat and Human P450 CYP3A: Possible Involvement of Non-Flavonoid Components in Drug Interaction.