Abstract

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.