Abstract
An ultraviolet spectrophotometric method has been devised for the determination of 5,5-dimethyl-2,4-oxazolidinedione ("DMO") in plasma.
After administration of 3,5,5-trimethyl-2,4-oxazolidinedione (trimethadione, Tridione) to dogs, the concentration of DMO in the plasma continues to rise for many hours and thereafter falls slowly. The maximum concentration attained is nearly equal to that resulting from administration of the same molar dose of DMO itself. It is inferred that demethylation of trimethadione by the dog is nearly complete.
Repeated oral dosage of trimethadione to a man for a period of six days brought about progressive accumulation of DMO in the plasma. The subsequent elimination of the drug was remarkably slow. Calculations based on plasma concentrations lead to the conclusion that conversion of trimethadione to DMO is essentially complete in man and that chronic administration results in the presence in the body of much larger amounts of the demethylated product than of the unchanged drug.
Small amounts of DMO were isolated from the urine of the man and identified.
The possibility is discussed that DMO may play some part in the therapeutic or toxic effects resulting from the clinical use of trimethadione.
Footnotes
- Received November 28, 1952.
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