THE EFFECT OF DICUMAROL ON PROTHROMBIN TIME IN RATS AND ITS RELATION TO VITAMIN K CONTENT OF LIVER

Abstract

On administration of varying doses of vitamin K1 (2-methyl-3-phytyl-1,4-naphthoquinone) and vitamin K3 (2-methyl-1,4-naphthoquinone) to dicumarol-treated rats, it was observed that vitamin K1 at a low dosage strongly counteracted the dicumarol effect as measured by prothrombin time. The rate of lowering of prothrombin time depended upon the dose of vitamin K1 administered. Vitamin K3 did not counteract dicumarol even at a high dosage. In experiments with radioactive vitamin K1 in rats treated with dicumarol, it was observed that a positive correlation exists between the amount of radioactivity present in the liver and the shortening of prothrombin time in the animals.Rats showed wide individual variations in their response to dicumarol. This response could be altered by changing the dosage. The animals did not develop any particular tolerance to dicumarol on 3-day courses of this drug when the courses were repeated twice at 3-week intervals.Rats that were well fed and received dicumarol daily for 10 days acquired tolerance to the drug after 2 days as judged by prothrombin time values. Partial starvation in dicumarol-fed rats prolonged the prothrombin times and increased the percentage mortality. Results obtained in other work in this laboratory suggest that partial starvation probably constitutes a stress.