Simultaneous intake of grapefruit juice, but not other fruit beverages, is now known to alter pharmacokinetics and efficacies of various drugs.. Although drugs described above do not relate structurally with each other, a form of cytochrome P450 (CYP) 3A4, is shown to be responsible for the metabolisms of these drugs. The exact mechanism of this interaction remains yet unclear, but the suppression of drug metabolisms has been suggested as a major mechanism. We have isolated four components from grapefruit juice that inhibit human CYP3Amediated drug oxidation. The structures of these components were identified as furocoumarin derivatives by absorption spectra, APCI-LC/MS/MS and NMR after their purification by a reversed-phase HPLC. These furocoumarins are strong candidates for causative agents of grapefruit juice-mediated drug interaction, because of their inhibition equal or stronger than did a typical CYP3A4 inhibitor, ketoconazole, on microsomal testosterone 6β-hydroxylation in human livers.
