METABOLIC DEMETHYLATION OF 3,5-DIMETHYL-5-ETHYL 2,4-OXAZOLIDINEDIONE (PARAMETHADIONE, PARADIONE)

¹ Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina

The metabolic conversion of paramethadione to 5-ethyl-5-methyl-2, 4-oxazolidinedione ("EMO") has been studied in the dog and in man.

An analytical method for the determination of EMO in plasma is described.

The resolution of EMO is described.

EMO has been isolated from the urine of dogs after administration of paramethadione as well as of EMO itself. There is a slight preponderance of the levorotatory isomer.

After a single dose of paramethadione to a dog EMO appears in the plasma, increases in concentration for 1 to 2 days, and thereafter slowly disappears. Comparison of the concentrations of EMO attained when paramethadione and when EMO itself are administered indicates that the dog demethylates paramethadione to a large extent.

Chronic oral administration of paramethadione to man results in progressive accumulation of EMO in the plasma. Calculations derived from plasma concentrations of EMO indicate that man converts paramethadione almost completely to EMO.

The therapeutic role of EMO in the clinical use of paramethadione is discussed.