RT Journal Article
SR Electronic
T1 KINETICS OF ANTICOAGULANT EFFECT OF DICUMAROL IN RATS
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 253
OP 260
VO 184
IS 1
A1 LEMUEL B. WINGARD, JR.
A1 GERHARD LEVY
YR 1973
UL http://jpet.aspetjournals.org/content/184/1/253.abstract
AB The purposes of this study were 1) to determine the relationship between plasma-dicumarol concentration and anticoagulant effect in rats and 2) to compare the kinetics of the anticoagulant effect of dicumarol in the rat and man. Special methodology was developed for repeated determination of dicumarol concentration and prothrombin complex activity in individual animals. The inhibition of prothrombin complex activity synthesis rate at any time could be related quantitatively to the dicumarol concentration in the plasma. This permits a quantitative description of the time course of the anticoagulant effect in relation to the elimination kinetics of dicumarol. There are quantitative differences between rats and man in the pharmacokinetic constants for dicumarol elimination, for synthesis and degradation of vitamin K-dependent clotting factors as reflected by prothrombin complex activity and for the relationship between drug concentration and effect, but the pharmacokinetic relationships are basically the same. Consequently, the rat can be a useful animal model for studying various drug interactions and other factors which modify the activity of coumarin anticoagulants. © 1973 by The Williams & Wilkins Company