title: Effect of rutin on warfarin anticoagulation and pharmacokinetics of warfarin enantiomers in rats.
abstract: OBJECTIVE
  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).
  
  
  RESULTS
  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.
authors.affiliation: Department of Pharmacy, National University of Singapore, Singapore, Republic of Singapore. phaelic@nus.edu.sg
authors.forename: Eli
authors.initials: E
authors.lastname: Chan
authors.forename: Akhil
authors.initials: A
authors.lastname: Hegde
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects*; D001798:Blood Proteins / Q000378:metabolism; D004347:Drug Interactions; D008297:Male; D011485:Protein Binding / Q000187:drug effects; D011794:Quercetin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012431:Rutin / Q000494:pharmacology*; D013237:Stereoisomerism; D014859:Warfarin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*
chemical_list: D000925:Anticoagulants; D001798:Blood Proteins; D012431:Rutin; D014859:Warfarin; D011794:Quercetin