EFFECTS OF LIVER INJURY AND NEPHRECTOMY ON THE ANTICONVULSANT ACTIVITY OF OXAZOLIDINE-2,4-DIONES

¹ Departments of Pharmacology, University of Utah College of Pharmacy and College of Medicine, Salt Lake City, Utah

Trimethadione and paramethadione were tested at various time intervals after their administration in normal, liver-injured and nephrectomized rats for their ability to prevent the tonic extensor component of maximal electroshock seizures. The results were analyzed for the effect of liver injury and nephrectomy on the potency and the duration of anticonvulsant action of these compounds. Liver injury significantly increased the potency and the duration of action of both drugs. On the other hand, bilateral nephrectomy increased the potency and the duration of action only of paramethadione; within the time intervals employed, this procedure had no significant effect on the anticonvulsant properties of trimethadione.

The results suggest that, in the rat, the liver is the principal organ for the degradation of trimethadione into products devoid of anticonvulsant action, and that the kidney plays no important role in the metabolic alteration or excretion of this compound; in contrast, both the liver and the kidney appear to be concerned in the degradation and elimination of paramethadione.