Abstract
The biological half-life of warfarin in a group of male Sprague–Dawley rats varied from 5 to 28hr, and the apparent volume of distribution varied from 102 to 320 ml/kg body weight. There was a strong and statistically highly significant positive correlation between the elimination rate constant and the apparent volume of distribution of warfarin in individual rats. There was no relationship between the elimination rate constant for warfarin and either the normal (prewarfarin) prothrombin complex activity or the rate constant for decline of this activity when the synthesis of vitamin K-dependent clotting factors was blocked. The concentration of warfarin in plasma at which the synthesis rate of prothrombin complex activity was inhibited by 50% varied from 0.05 to 1.37 μg/ml and showed a strong and highly statistically significant positive correlation with the biological half-life of warfarin in individual animals. These results demonstrate a pronounced association among the apparent volume of distribution, the elimination rate constant, and the plasma concentration-anticoagulant effect relationship for warfarin which may have to be considered in the design of clinical dosage regimens.
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