Key result
Warfarin clearance correlates strongly with free plasma fraction, with required doses declining with age.
Observational (n=15)
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1 The relationship between warfarin dose, total and free plasma warfarin concentration, and anticoagulant effect was examined at several steady-state levels in fifteen patients during withdrawal of warfarin therapy. 2 Total plasma clearance was significantly correlated with the free fraction in plasma (r=0.955). 3 There was an age related decline in the dose of warfarin, and in the total and free plasma warfarin concentrations required to produce the same anticoagulant effect. However, neither total nor free plasma warfarin clearances varied with age. 4 Individual patients' log concentration-effect relationships were linear above a prothrombin ratio of 1.2 and there was a significant correlation (r=-0.586) between the slope and the free fraction of warfarin in plasma. It is suggested that plasma protein binding may reflect the interaction between warfarin and its effector site in the hepatocyte.
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Routledge et al. (1979) conducted an observational in Patients on warfarin therapy (n=15). Warfarin was evaluated on Relationship between warfarin dose, plasma concentration, and anticoagulant effect (r=0.955). Warfarin total plasma clearance was significantly correlated with its free fraction in plasma (r=0.955), and the dose required for a given anticoagulant effect declined with age.
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