Inhibitory effect of natural furanocoumarins on human microsomal cytochrome P450 3A activity

To investigate the possible drug interaction with herbal medicine, furanoco umarin derivatives isolated from several Umbelliferous crude drugs were exa mined for their inhibitory effects on a typical human drug metabolizing enz yme, cytochrome P450 3A (CYP3A). Most furanocoumarins tested at 0.1 mM redu ced microsomal testosterone 6 beta-hydroxylation as an index of CYP3A activ ity to less than 50% of the central. In particular, the dimer and trimer de rivatives of furanocoumarins showed striking inhibition, whose potencies we re similar to that of a typical CYP3A inhibitor, ketoconazole. Preincubatio n of dimer types of furanocoumarins increased suppression but not most of t he monomer derivatives, suggesting that the inhibition on CUP3A activity wa s caused by at least plural mechanisms. These results raised the possibilit y that the furanocoumarin containing herbal medicines may alter pharmacokin etics of co-ingested drugs similar to the case with grapefruit juice.