THE PHYSIOLOGICAL DISPOSITION OF ETHYL BISCOUMACETATE (TROMEXAN) IN MAN AND A METHOD FOR ITS ESTIMATION IN BIOLOGICAL MATERIAL

¹ Section on Chemical Pharmacology, National Heart Institute, National Institutes of Health, Public Health Service, Federal Security Agency, Bethesda, Maryland and the Research Service, Third (New York University) Medical Division, Goldwater Memorial Hospital, New York, New York

1. A method is described for the estimation of Tromexan in biological fluids and tissues.

2. Tromexan is rapidly and essentially completely absorbed from the gastrointestinal tract, compared to the slow and sometimes incomplete absorption of Dicumarol.

3. The biotransformation of Tromexan is rapid, averaging about 25 per cent hourly, compared to Dicumarol, which averages about 40 per cent daily. As with Dicumarol, the rate of metabolic transformation varies widely in different subjects. The rate also depends on the dose, the smaller doses being metabolized at a faster rate.

4. After a single dose, Tromexan practically disappears from the body before the prothrombin response becomes evident. Single daily doses of the drug result in detectable plasma concentrations for only a few hours each day, but the prothrombin response is cumulative and reaches a plateau after several days of therapy.

5. Wide individual differences in response to Tromexan occur. There is little correlation between the persistence of the drug in the body and the peak prothrombin response.

6. Sudden unpredictable changes in prothrombin time frequently occur in subjects receiving regular daily doses of Tromexan. Correction of these changes by readjusting dosage is frequently difficult.