Comparative Pharmacokinetics of Coumarin Anticoagulants II: Pharmacokinetics of Bishydroxycoumarin Elimination in the Rat, Guinea Pig, Dog, and Rhesus Monkey

Low (1–2mg./Kg.) and high (8–20mg./Kg.) doses of bishydroxycoumarin (BHC) were administered intravenously in cross-over fashion to rats (Sprague-Dawley, male), guinea pigs (Hartley, male), dogs (beagle and mongrel, male and female), and monkeys (rhesus, male). BHC levels in the plasma declined expon...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 1968-01, Vol.57 (1), p.68-71
Main Authors: Nagashima, Renpei, Levy, Gerhard, Back, Nathan
Format: Article
Language:English
Subjects:
Alkanes
Animals
Biologic half-life of bishydroxycoumarin
Biological Assay
Bishydroxycoumarin determination in plasma
Coumarin anticoagulants
Dicumarol - blood
Dicumarol - metabolism
Dogs
Female
Guinea Pigs
Haplorhini
Heptane extraction
Kinetics
Male
Pharmacokinetics of bishydroxycoumarin elimination
Rats
Solvents
Species Specificity
Spectrophotometry
UV analysis
Volume of distribution-apparent
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Summary:Low (1–2mg./Kg.) and high (8–20mg./Kg.) doses of bishydroxycoumarin (BHC) were administered intravenously in cross-over fashion to rats (Sprague-Dawley, male), guinea pigs (Hartley, male), dogs (beagle and mongrel, male and female), and monkeys (rhesus, male). BHC levels in the plasma declined exponentially with time in each species. The size of the dose had no significant effect on half-life in rats and guinea pigs. The half-life was variable in the dog and increased with increasing dose in the monkey. There was no pronounced change in the apparent volumes of distribution of BHC with dose in any of the animal species studied. The rat, guinea pig, and monkey eliminate BHC considerably more rapidly, while the dog eliminates the drug more slowly than man.
ISSN:0022-3549
1520-6017
DOI:10.1002/jps.2600570113