title: A pilot study of the association of pharmacokinetic and pharmacodynamic parameters of warfarin with the dose in patients on long-term anticoagulation.
abstract: BACKGROUND
  Warfarin is a widely used anticoagulant with a low therapeutic index. There is wide interindividual variation in the pharmacokinetics and pharmacodynamics of warfarin which is also reflected in the warfarin dose requirement. CYP2C9 and VKORC1 polymorphisms have been shown to affect warfarin dose requirement. However a large amount of the variation in warfarin dose remains unaccounted for.
  
  
  CONCLUSIONS
  Our findings suggest that in patients who are on long-term warfarin therapy, INR : plasma 7-hydroxywarfarin concentration correlates well with warfarin requirement and also accounts for a large amount of variation in warfarin dose.
  
  
  OBJECTIVE
  To assess the correlation between plasma total warfarin concentration, plasma 7-hydroxywarfarin concentration and INR and the weekly doses of warfarin in patients on long-term anticoagulation.
  
  
  METHODS
  Twenty-five patients on long-term anticoagulation with warfarin were studied. Plasma total warfarin and 7-hydroxywarfarin concentrations and INR were determined. Equations were derived with the weekly warfarin dose as the dependent variable and plasma total warfarin concentration : plasma 7-hydroxywarfarin concentration, INR : plasma total warfarin concentration and INR : plasma 7-hydroxywarfarin concentration as independent variables.
  
  
  RESULTS
  There was a good correlation between INR : plasma total warfarin concentration and the weekly dose of warfarin (y = 46.73e(-0.30x), r(2) = 0.65). There was a better correlation between INR : plasma 7-hydroxywarfarin concentration and the weekly dose of warfarin (y = 156.52x(-0.63), r(2) = 0.74)
  
  
  CONCLUSIONS
  Pharmacokinetic parameters along with INR seem to correlate with the weekly doses of warfarin in patients on long-term anticoagulation. These parameters may therefore be useful for predicting warfarin doses.
authors.affiliation: Department of Clinical Pharmacology, Seth GS Medical College and KEM Hospital, Parel, Mumbai 400012, India.
authors.forename: Uday P
authors.initials: UP
authors.lastname: Kulkarni
authors.forename: Balkrishna D
authors.initials: BD
authors.lastname: Swar
authors.forename: Dilip R
authors.initials: DR
authors.lastname: Karnad
authors.forename: Sanish
authors.initials: S
authors.lastname: Davis
authors.forename: Anil M
authors.initials: AM
authors.lastname: Patwardhan
authors.forename: Nilima A
authors.initials: NA
authors.lastname: Kshirsagar
authors.forename: Nithya J
authors.initials: NJ
authors.lastname: Gogtay
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D008134:Long-Term Care; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D014859:Warfarin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D000925:Anticoagulants; D014859:Warfarin