JPET

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by WEINER, M.
Right arrow Articles by BRODIE, B. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by WEINER, M.
Right arrow Articles by BRODIE, B. B.
Journal of Pharmacology And Experimental Therapeutics, Vol. 99, Issue 4, 409-420, 1950
Copyright © 1950 by American Society for Pharmacology and Experimental Therapeutics

THE PHYSIOLOGICAL DISPOSITION OF DICUMAROL IN MAN

MURRAY WEINER 1, SHEPARD SHAPIRO 1, JULIUS AXELROD 1, JACK R. COOPER 1, and BERNARD B. BRODIE 1

1 Research and Medical Services, Third (New York University) Medical Division, Goldwater Memorial Hospital; Department of Biochemistry, New York University College of Medicine; National Heart Institute, National Institutes of Health, Bethesda, Maryland

1. Dicumarol is slowly metabolized in man to unknown transformation products. The drug is extensively localized on the proteins of plasma and in other body tissues. The resulting low free plasma level explains, in part, its slow rate of transformation, as well as its negligible rate of elimination by the kidneys.

2. The drug is slowly and erratically absorbed from the gastrointestinal tract. There is considerable variation in the absorption rate in different subjects. Furthermore, the small doses are absorbed more quickly than large ones.

3. The rate of transformation of the drug is widely divergent for different subjects. The rate also depends on the dose, the smaller doses being metabolized at a faster rate.

4. For each subject there is a threshold plasma level of Dicumarol which must be reached before a detectable prothrombin response is elicited. This level varies from subject to subject but is generally between 5 and 10 mgm. per liter. There is a considerable lag between maximal plasma level and maximal prothrombin time response to the drug.

5. The duration of the prothrombin time response is a function of the persistence of Dicumarol in the plasma. However, for a given plasma level of the substance, the elevation in prothrombin time varies widely among subjects.

Submitted on March 30, 1950




This article has been cited by other articles:


Home page
 ScienceHome page
E. S. Vesell and J. G. Page
Genetic Control of Drug Levels in Man: Antipyrine
Science, July 5, 1968; 161(3836): 72 - 73.
[Abstract] [PDF]

Home page
 ScienceHome page
E. S. Vesell and J. G. Page
Genetic Control of Drug Levels in Man: Phenylbutazone
Science, March 29, 1968; 159(3822): 1479 - 1480.
[Abstract] [PDF]

Home page
 ANGIOLOGYHome page
R. E. Fremont
Pharmacodynamics of Parenteral and Oral Anticoagulants
Angiology, March 1, 1964; 15(3): 152 - 162.
[PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1950 by the American Society for Pharmacology and Experimental Therapeutics.