Dicumarol Labelled with C 14 . ∗

Abstract

Summary

Dicumarol, containing C¹⁴ in the methylene bridge was synthesized and given intravenously to mice and rabbits. The activity disappeared rapidly from the blood and was recovered in the liver, bile, intestinal contents and later in the urine, but not from other tissues. About 10% of the activity became fixed in the liver. It was demonstrated by isolation using the isotope dilution technique that this activity was due to unchanged dicumarol. This dicumarol remained fixed in the mouse liver for 16 hours, in rabbit liver for 3 days. The corresponding duration of hypoprothrombinemia was 4 days and 9 days. The presence of extra vitamin K resulted in the dicumarol disappearing more rapidly from the liver. It is suggested that the period of time that dicumarol remains in the liver is related to the effectiveness of the agent in interfering with the formation of prothrombin. Dicumarol was not excreted by the kidney but evidence of excretion of metabolic products was found in the urine and feces for the mouse and in the urine only for the rabbit.