Potency and Coagulation Factor Effects of 2,3,5,6-Tetrachloro-4-pyridinol Compared to Warfarin and Its Antagonism by Vitamin K

Abstract

Summary

The potency of 2,3,5, 6-tetrachloro-4-pyridinol (TCP) was compared to that of warfarin sodium in which the drugs were administered intragastrically to rats and 1-stage prothrombin times were determined 48 hr later. TCP was found to have 2.25% the potency of warfarin sodium. Both compounds were found to produce unclottable plasmas in the 1-stage prothrombin time test when larger doses were administered.

Studies in beagle dogs, using single oral doses of TCP and warfarin sodium, were done to determine the effects of the drugs on various coagulation factors. Both compounds produced a lowering in the activities of prothrombin, factors VII + ×, factor ×, and factor IX. No significant alterations in factor V activity or in plasma fibrinogen concentration were found. The peak effects were usually reflected in the 41 hr post drug blood samples and pre-drug or near pre-drug values were approached at 161 hr post drug.

Menadione sodium bisulfite (vitamin K₃) and phytonadione (vitamin K₁) were found to be effective antagonists to the effects produced on 1-stage prothrombin time when TCP sodium was administered to rats. Phytonadione was found to be 52% more effective than menadione sodium bisulfite in this activity.

The author gratefully acknowledges the technical assistance of D. R. Christian, E. N. Massad and J. F. Williams.