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Ngo N, Brantley SJ, Carrizosa DR, et al. The warfarin-cranberry juice interaction revisited: A systematic in vitro-in vivo evaluation. J Exp Pharmacol. 2010;2010(2):83-91doi: 10.2147/JEP.S11719.
Ngo, N., Brantley, S. J., Carrizosa, D. R., Kashuba, A. D., Dees, E. C., Kroll, D. J., Oberlies, N. H., & Paine, M. F. (2010). The warfarin-cranberry juice interaction revisited: A systematic in vitro-in vivo evaluation. Journal of experimental pharmacology, 2010(2), 83-91. https://doi.org/10.2147/JEP.S11719
Ngo, Ngoc, et al. "The warfarin-cranberry juice interaction revisited: A systematic in vitro-in vivo evaluation." Journal of experimental pharmacology vol. 2010,2 (2010): 83-91. doi: https://doi.org/10.2147/JEP.S11719
Ngo N, Brantley SJ, Carrizosa DR, Kashuba AD, Dees EC, Kroll DJ, Oberlies NH, Paine MF. The warfarin-cranberry juice interaction revisited: A systematic in vitro-in vivo evaluation. J Exp Pharmacol. 2010 Jul;2010(2):83-91. doi: 10.2147/JEP.S11719. PMID: 20865058; PMCID: PMC2943398.
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J Exp Pharmacol. 2010 Jul;2010(2):83-91. doi: 10.2147/JEP.S11719.

The warfarin-cranberry juice interaction revisited: A systematic in vitro-in vivo evaluation.

Journal of experimental pharmacology

Ngoc Ngo, Scott J Brantley, Daniel R Carrizosa, Angela Dm Kashuba, E Claire Dees, David J Kroll, Nicholas H Oberlies, Mary F Paine

Affiliations

  1. UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

PMID: 20865058 PMCID: PMC2943398 DOI: 10.2147/JEP.S11719

Abstract

BACKGROUND: Cranberry products have been implicated in several case reports to enhance the anticoagulant effect of warfarin. The mechanism could involve inhibition of the hepatic CYP2C9-mediated metabolic clearance of warfarin by components in cranberry. Because dietary/natural substances vary substantially in bioactive ingredient composition, multiple cranberry products were evaluated in vitro before testing this hypothesis in vivo. METHODS: The inhibitory effects of five types of cranberry juices were compared with those of water on CYP2C9 activity (S-warfarin 7-hydroxylation) in human liver microsomes (HLM). The most potent juice was compared with water on S/R-warfarin pharmacokinetics in 16 healthy participants given a single dose of warfarin 10 mg. RESULTS: Only one juice inhibited S-warfarin 7-hydroxylation in HLM in a concentration-dependent manner (P < 0.05), from 20% to >95% at 0.05% to 0.5% juice (v/v), respectively. However, this juice had no effect on the geometric mean AUC(0-∞) and terminal half-life of S/R-warfarin in human subjects. CONCLUSIONS: A cranberry juice that inhibited warfarin metabolism in HLM had no effect on warfarin clearance in healthy participants. The lack of an in vitro-in vivo concordance likely reflects the fact that the site of warfarin metabolism (liver) is remote from the site of exposure to the inhibitory components in the cranberry juice (intestine).

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