Influence of Spironolactone and other Steroids on the Enzymatic Decay and Anticoagulant Activity of Bishydroxycoumarin

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Abstract
In rats, pretreatment with spironolactone, norbolethone or ethylestrenol enhances the disappearance of bishydroxycoumarin from blood and restores prothrombin time to almost normal whereas triamcinolone or progesterone fail to do so. In itself SKF 525-A does not influence prothrombin time, but it markedly increases the blood concentration and the anticoagulant activity of bishydroxycoumarin. Furthermore, this microsomal enzyme-inhibitor suppresses the decrease of blood bishydroxycoumarin concentration elicited by ethylestrenol. Pretreatment with spironolactone or ethylestrenol (but not with progesterone) enhances the NADPH-dependent enzymatic decay of bishydroxycoumarin in liver microsomal + supernatant fraction. The elimination of bishydroxycoumarin from blood is reduced if its administration is followed by subsequent treatment with norbolethone, progesterone, ethylestrenol or triamcinolone. These findings suggest that great care should be exercised in patients on anticoagulant therapy and treated previously or conjointly with various steroids ; in dubious cases not only prothrombin time but also the blood concentration of the anticoagulant should be checked. * This work was supported by grants from the Ministère de la Santé, Québec, and from the Medical Research Council of Canada (Block Term Grant MT-1829). The authors are also indebted to the suppliers mentioned in the ‘Materials and Methods’ section for their generous donation of the drugs used in these experiments. The technical assistance of Mrs. Claudie Jubert and Miss Eliane Aclément is hereby acknowledged.

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