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Title: Effect of rutin on warfarin anticoagulation and pharmacokinetics of warfarin enantiomers in rats
Authors: Chan, E. 
Hegde, A.
Chen, X.
Keywords: Pharmacodynamics
Stereoselective drug interactions
Issue Date: Apr-2009
Citation: Chan, E., Hegde, A., Chen, X. (2009-04). Effect of rutin on warfarin anticoagulation and pharmacokinetics of warfarin enantiomers in rats. Journal of Pharmacy and Pharmacology 61 (4) : 451-458. ScholarBank@NUS Repository.
Abstract: Objectives: The effects of the flavonoid rutin on the anticoagulant activity of oral warfarin and the protein binding and pharmacokinetics of its enantiomers were investigated in rats. Methods: A single dose of racemic warfarin, 1.5 mg/kg, was administered orally to rats either alone or on day 5 of an 8-day oral regimen of rutin, 1 g/kg daily. Results: Rutin reduced the anticoagulant effect of racemic warfarin, evident as a 31% reduction in the area under the prothrombin complex activty - time curve (P < 0.05). Key findings: Rutin had no apparent effect on pre-treatment baseline blood coagulation. It enhanced the in-vitro serum protein binding of S- and R-warfarin (reflected by 40% and 26% reductions in unbound fraction, respectively), and thus restricted distribution by 33 and 21%, respectively. Treatment with rutin significantly decreased the elimination half-life of S-warfarin by 37% as a result of the 69% increase in unbound clearance of the S-enantiomer. This effect was attributed to a significant 77% increase in the unbound formation clearance of the overall oxidative and reductive metabolites, and an increase in the unbound renal clearance of the more potent S-enantiomer of warfarin. Conclusions: Concurrent rutin administration is likely to reduce the anticoagulant effect of racemic warfarin, reflecting a significant decrease in the elimination half-life of the more potent S-enantiomer. © 2009 The Authors.
Source Title: Journal of Pharmacy and Pharmacology
ISSN: 00223573
DOI: 10.1211/jpp/61.04.0006
Appears in Collections:Staff Publications

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