GRAPEFRUIT COMPONENT INTERACTING WITH RAT AND HUMAN P450 CYP3A - POSSIBLE INVOLVEMENT OF NONFLAVONOID COMPONENTS IN DRUG-INTERACTION

Active components in grapefruit juice, which modulate a cytochrome P45 0 (CYP3A) activity, were investigated. CYP3A-catalyzed 6 beta-hydroxyl ation of testosterone in livers of rat and human was inhibited by the addition of an ethyl acetate-extract of grapefruit juice. Several comp onents of grapefruit juice, including naringin, naringenin, limonin an d 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. Analy ses with HPLC indicate the existence of inhibitory components in the e xtract, which are distinct from these known compounds and are specific to grapefruit juice. These results suggest that hydrophobic component s other than flavonoids, probably coumarin derivatives, are responsibl e for the inhibitory effect of grapefruit juice.