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Article
August 1954

CLINICAL EXPERIENCE WITH COUMARIN ANTICOAGULANTS WARFARIN AND WARFARIN SODIUM

Author Affiliations

MADISON, WIS.

From the Department of Medicine, University of Wisconsin Medical School.

AMA Arch Intern Med. 1954;94(2):213-220. doi:10.1001/archinte.1954.00250020047003
Abstract

SYNTHESIS of the 3-substituted-4-hydroxycoumarin anticoagulant No. 42, 3-(a phenyl-β-acetylethyl)-4-hydroxycoumarin,* was first accomplished and its action studied in Dr. Karl Paul Link's laboratory.† The compound has been generically termed "warfarin" and its sodium salt termed "warfarin sodium." The sodium derivative4 is readily water-soluble, and the solutions are stable. Structural formulae of these compounds appear in Figure 1. Warfarin, when given orally, and warfarin sodium, when given orally or intravenously, produce hypoprothrombinemia, as do the other 3-substituted-4-hydroxycoumarin compounds.

Interesting experimental data regarding warfarin sodium and warfarin in the rat have been made available by Eble,‡ working in Link's laboratory. These workers believe the rat to be the preferred experimental animal in the study of 4-hydroxycoumarin anticoagulants, as the response of the rat is most closely parallel to that of the human. Eble found that when massive oral doses, of 100 mg. per kilogram, of warfarin were given the rat

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