EFFECT OF WARFARIN ON KINETICS OF VITAMIN K-DEPENDENT CLOTTING FACTORS IN RATS

  • 1 January 1977
    • journal article
    • research article
    • Vol. 201  (2) , 507-517
Abstract
The time course of activities and rates of synthesis of activities for the separate clotting factors II, VII, IX and X were compared and the rate of synthesis of activity of each factor was related to the plasma concentration of warfarian in individual rats after acute and chronic dosing with warfarin. Sequences of blood samples were obtained from each rat by 50-70 h after an acute dose of warfarin or for 120 h after a chronic loading dose plus 12 h maintenance doses of warfarin and assayed for factor activities and warfarin concentration. The half-lives for degradation of factor activities ranged from 2.6-9.0 h for the 4 factors. During periods of changing warfarin concentration (acute dosing) factor VII and X activities and rates of synthesis of activity showed large rapid changes, while factors II and IX responded more slowly. As the warfarin concentration diminished, the factor X rate of synthesis of activity appeared to exceed predrug values in all rats. During chronic dosing with warfarin the factor II activity and rate of synthesis of activity for each factor was related linearly to the logarithm of the plasma concentration of warfarin for the range 0-80% depression with acute dosing. However, this relationship was not suitable to explain the apparent overshoot in factor X rate of synthesis of activity.