Cranberry (Vaccinium macrocarpon Ait., Ericaceae), distributed in North America, has traditionally been used in the treatment and prevention of urinary tract infections. Various types of constituents including terpenoids, iridoids, and polyphenols, such as proanthocyanidins, anthocyanins, flavonoids, and organic acids are contained in cranberry. Among them, A-type proanthocyanidins have been revealed to inhibit the adherence of uropathogenic P-fimbriated Escherichia coli to eukaryotic cells, and this is thought to be the mechanism underlying its role in preventing urinary tract infection. However, some case reports showed the interaction between cranberry and warfarin. [1, 2] The possible interaction of cranberry with warfarin was suggested to depend on the inhibition of cytochrome P450 (CYP) activities, which is involved in most metabolism-mediated drug interaction. We recently reported the inhibitory effect of 60 polyphenols on CYP3A4 and CYP2C9 activity, indicating that some cranberry flavonoids can significantly inhibit these CYPs [3] In this study, we investigated CYP3A4 and CYP2C9 inhibitory activities of cranberry juice constituents and their metabolites. The bioassay-guided fractionation of cranberry extracts gave the cranberry-derived proanthocyanidin polymer (CPP) as the most potent inhibitor of CYP3A4 and CYP2C9. Furthermore, we investigated the plasma level of warfarin and alternation in international normalized ratio after ingestion of CPP or cranberry juice (CJ) to rats, indicating that co-administration of CJ was unlikely to affect the pharmacokinetics and pharmacodynamics of warfarin in rats. Further investigation and improved case studies are needed to address these issues.
References: 1. Committee on Safety of Medicines, Medicines and Healthcare Products Regulatory Agency. Possible interaction between warfarin and cranberry juice. (2003) Curr. Probl. Pharmacovigil. 29:8.
2. Suvarna, R. et al. Possible interaction between warfarin and cranberry juice. (2003) BMJ. 327:1454.
3. Kimura, Y. et al. (2010) Food Chem. Toxicol. 48:429–435.
