| Autor: |
Ngo, Ngoc, Brantley, Scott J, Carrizosa, Daniel R, Kashuba, Angela DM, Dees, E Claire, Kroll, David J, Oberlies, Nicholas H, Paine, Mary F |
| Jazyk: |
angličtina |
| Rok vydání: |
2010 |
| Předmět: |
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| Zdroj: |
Journal of Experimental Pharmacology |
| ISSN: |
1179-1454 |
| Popis: |
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 (P0.05), from 20% to95% 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). |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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