Document Detail


Pharmacodynamic interaction of warfarin with cranberry but not with garlic in healthy subjects.
MedLine Citation:
PMID:  18516070     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND PURPOSE: Patients commonly take complementary medicines in conjunction with warfarin yet evidence supporting the safety or the risk of a herb-drug interaction is lacking. The aim of this study was to investigate the possible impact of two commonly used herbal medicines, garlic and cranberry, on the pharmacokinetics and pharmacodynamics of warfarin in healthy male subjects.
EXPERIMENTAL APPROACH: An open-label, three-treatment, randomized crossover clinical trial was undertaken and involved 12 healthy male subjects of known CYP2C9 and VKORC1 genotype. A single dose of 25 mg warfarin was administered alone or after 2 weeks of pretreatment with either garlic or cranberry. Warfarin enantiomer concentrations, INR, platelet aggregation and clotting factor activity were measured to assess pharmacokinetic and pharmacodynamic interactions between warfarin and herbal medicines.
KEY RESULTS: Cranberry significantly increased the area under the INR-time curve by 30% when administered with warfarin compared with treatment with warfarin alone. Cranberry did not alter S- or R-warfarin pharmacokinetics or plasma protein binding. Co-administration of garlic did not significantly alter warfarin pharmacokinetics or pharmacodynamics. Both herbal medicines showed some evidence of VKORC1 (not CYP2C9) genotype-dependent interactions with warfarin, which is worthy of further investigation.
CONCLUSIONS AND IMPLICATIONS: Cranberry alters the pharmacodynamics of warfarin with the potential to increase its effects significantly. Co-administration of warfarin and cranberry requires careful monitoring.
Authors:
M I Mohammed Abdul; X Jiang; K M Williams; R O Day; B D Roufogalis; W S Liauw; H Xu; A J McLachlan
Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2008-06-02
Journal Detail:
Title:  British journal of pharmacology     Volume:  154     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-08-11     Completed Date:  2008-09-30     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1691-700     Citation Subset:  IM    
Affiliation:
Faculty of Pharmacy, University of Sydney, Sydney, New South Wales, Australia.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Anticoagulants / pharmacokinetics,  pharmacology*
Aryl Hydrocarbon Hydroxylases / genetics
Cross-Over Studies
Drug Monitoring
Garlic / chemistry*
Genotype
Herb-Drug Interactions
Humans
International Normalized Ratio
Male
Mixed Function Oxygenases / genetics
Platelet Aggregation / drug effects
Protein Binding / drug effects
Stereoisomerism
Time Factors
Vaccinium macrocarpon / chemistry*
Warfarin / pharmacokinetics,  pharmacology*
Chemical
Reg. No./Substance:
0/Anticoagulants; 81-81-2/Warfarin; EC 1.-/Mixed Function Oxygenases; EC 1.14.14.1/Aryl Hydrocarbon Hydroxylases; EC 1.14.14.1/CYP2C9 protein, human; EC 1.14.99.-/vitamin K epoxidase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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