STUDY OF THE INTERACTION OF BARBITURATES AND DICUMAROL AND THEIR EFFECT ON PROTHROMBIN ACTIVITY, HEMORRHAGE, AND SLEEPING TIME IN RATS

Abstract

In this study the influence of barbiturates (Nembutal and Barbitone) upon the pharmacological activity of Dicumarol and the converse interaction were evaluated. Prothrombin time, incidence of hemorrhage, and sleeping time were measured in relation to the pharmacological action of each drug when given simultaneously and separately. Groups of Sprague–Dawley, white, male rats weighing approximately 250–350 g were fed Dicumarol, barbiturates, or the combination of both mixed with powdered food during the 10 days of the experiment. Groups treated with Dicumarol plus barbiturates showed a significantly shorter mean prothrombin time and lower incidence of hemorrhage than the group treated with Dicumarol alone. When the combination of drugs or each drug alone was administered by stomach tube or intraperitoneally, similar findings were obtained. Barbiturates exerted a protective action against the hypoprothrombinemic and hemorrhagic effects of even a toxic dose of Dicumarol, regardless of the route of administration. The mean sleeping time of groups treated with Nembutal alone was not significantly different from that of groups treated with Nembutal–Dicumarol. No hemorrhage was observed in the control animals or those receiving barbiturates only, nor was there a difference in the mean prothrombin time of these groups.