CYP2C9 is involved in the metabolism of many drugs such as warfarin and phenytoin (PHT). It is well known that some foods cause pharmacokinetic alterations of drugs and lead to toxicity. Regarding the interaction caused by cranberry juice (CrJ), its influence on the metabolism of warfarin, a CYP2C9 substrate, is controversial. In addition, information concerning the influence of CrJ on the pharmacokinetics of other substrate drugs of CYP2C9 is not available. To examine the inhibitory effect of CrJ on the metabolism of PHT, we performed experiments using a baculovirus expression microsome system and human liver microsome assay. CrJ concentration-dependently inhibited the substrate metabolism both in a baculovirus-expressed microsome system and in human liver microsome assay. These data support the idea that CrJ inhibits CYP2C9 activity, and the subsequent metabolism of drugs metabolized by CYP2C9. In this study, we did not identify the specific substance(s) which inhibits CYP2C9 activity. However, as CrJ did not enhance the PHT accumulation in 3D-HepG2 cells, it is thought that the penetration into hepatic cells of inhibitory substances in CrJ seems to be small.

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