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Pharmacodynamic interaction of warfarin with cranberry but not with garlic in healthy subjects.

Abstract：

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.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Mohammed Abdul MI,Jiang X,Williams KM,Day RO,Roufogalis BD,Liauw WS,Xu H,McLachlan AJ

doi

10.1038/bjp.2008.210

subject

Has Abstract

pub_date

2008-08-01 00:00:00

pages

1691-700

issue

8

eissn

0007-1188

issn

1476-5381

pii

bjp2008210

journal_volume

154

pub_type

杂志文章,随机对照试验

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