A pilot study of the association of pharmacokinetic and pharmacodynamic parameters of warfarin with the dose in patients on long-term anticoagulation.
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.
Kulkarni
Uday P
UP
Department of Clinical Pharmacology, Seth GS Medical College and KEM Hospital, Parel, Mumbai 400012, India.
Swar
Balkrishna D
BD
Karnad
Dilip R
DR
Davis
Sanish
S
Patwardhan
Anil M
AM
Kshirsagar
Nilima A
NA
Gogtay
Nithya J
NJ
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
D000925:Anticoagulants; D014859:Warfarin