THE BIOTRANSFORMATION OF ETHYL BISCOUMACETATE (TROMEXAN) IN MAN, RABBIT AND DOG

¹ Third (New York University) Medical Division, Goldwater Memorial Hospital, New York, New York
² Laboratory of Chemical Pharmacology, National Heart Institute, National Institutes of Health, Public Health Service, Federal Security Agency, Bethesda, Maryland

1. Tromexan undergoes almost complete metabolic transformation in man. An important route of metabolism involves hydroxylation of one of the benzene rings. The metabolite, hydroxy-Tromexan, reaches the urine by a circuitous route; it is formed in the liver and secreted into the bile; it then passes into the intestine, and after absorption into the bloodstream is finally excreted in the urine. This accounts for the long delay before the metabolite appears in the urine; most of the administered Tromexan has disappeared from the body before the metabolite appears in the urine. There is no evidence for the hydrolysis of Tromexan in man to the corresponding acid, Tromexan acid.

2. Hydroxy-Tromexan does not affect the prothrombin activity of plasma in mice.

3. In the rabbit Tromexan is metabolized at about the same rate as in man, but by de-esterification rather than by hydroxylation.

4. In the dog, Tromexan is metabolized at a rate of about 3 per cent per hour, compared to about 20 per cent per hour in man and rabbit.