title: The warfarin-cranberry juice interaction revisited: A systematic in vitro-in vivo evaluation.
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).
authors.affiliation: UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Ngoc
authors.initials: N
authors.lastname: Ngo
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Brantley
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Carrizosa
authors.forename: Angela Dm
authors.initials: AD
authors.lastname: Kashuba
authors.forename: E Claire
authors.initials: EC
authors.lastname: Dees
authors.forename: David J
authors.initials: DJ
authors.lastname: Kroll
authors.forename: Nicholas H
authors.initials: NH
authors.lastname: Oberlies
authors.forename: Mary F
authors.initials: MF
authors.lastname: Paine