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Journal of Pharmacology And Experimental Therapeutics, Vol. 143, Issue 3, 273-277, 1964
Copyright © 1964 by American Society for Pharmacology and Experimental Therapeutics

THE NATURE OF THE ANTAGONISM BETWEEN VITAMIN K AND INDIRECT ANTICOAGULANTS

J. Lowenthal 1 and J. A. MacFarlane 1

1 Department of Pharmacology and Therapeutics, University of Manitoba Faculty of Medicine, Winnipeg, Canada

The simultaneous administration of an indirect anticoagulant, warfarin, inhibits partially or completely the increase of the plasma level of factor VII by an optimal dose of vitamin K1 in vitamin K-deficient, but not in anticoagulant pretreated rats. When the ratio of vitamin K1 to warfarin is kept constant, but the doses are increased, the inhibition at first increases, but disappears when the doses are increased further. The dose of vitamin K1 necessary for the disappearance of the inhibition is found to be constant for all dose ratios tested and of the same order of magnitude as that necessary to produce a comparable increase of the plasma level of factor VII in anticoagulant pretreated rats.

The results can be explained by the hypothesis that in addition to its normal site or mechanism of action, larger doses of vitamin K1 can act by an alternate site or mechanism. While indirect anticoagulants inhibit the action of vitamin K1 at the normal site by an antagonism which is not of the competitive, but either of the nonequilibrium (competitive irreversible) or noncompetitive type, larger doses of vitamin K1 reverse the inhibition by acting at the alternate site, which is not inhibited by indirect anticoagulants.

Submitted on August 20, 1963
Accepted on October 28, 1963




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Copyright © 1964 by the American Society for Pharmacology and Experimental Therapeutics.