title: Comparative pharmacokinetics of coumarin anticoagulants XV: relationship between pharmacokinetics of dicumarol and warfarin in rats.
abstract: The distribution, elimination, and anticoagulant effect of dicumarol and warfarin were determined in adult males rats following intravenous injection of single doses of these drugs in crossover experiments. The biological half-life of dicumarol ranged from 5 to 28 hr; that of warfarin ranged from 9 to 30 hr. There was a statistically significant correlation between the following pharmacokinetic characteristics of dicumarol and warfarin in individual animals: biological half-life, apparent volume of distribution, total plasma clearance, and concentration in plasma eliciting one-half the maximum anticoagulant effect (effective concentration). The mean ratio of the respective biological half-lives (warfarin/dicumarol) was 1.42, and that of the apparent volumes of distribution was 1.50. The ratio of the effective plasma concentrations (dicumarol/warfarin) was correlated negatively with the half-life of dicumarol and positively with the ratio of the half-life values (warfarin/dicumarol) in individual animals. Additional studies with serum samples from other rats showed pronounced interindividual differences in the serum protein binding of both dicumarol and warfarin and a strong correlation between the protein binding of these two drugs in serum of individual animals. The results of this study, together with the results of previous studies in this series, indicate that serum protein binding is the major determinant of interindividual differences in the pharmacokinetics of dicumarol and warfarin in rats under these experimental conditions.
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D001728:Dicumarol / Q000378:metabolism* / Q000494:pharmacology; D006207:Half-Life; D008297:Male; D011485:Protein Binding; D051381:Rats; D013696:Temperature; D014859:Warfarin / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D014859:Warfarin; D001728:Dicumarol