QUANTITATIVE STUDIES OF THE DEMETHYLATION OF N-METHYL BARBITAL (METHARBITAL, GEMONIL)

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

An analytical method is described for the simultaneous determination of N-methyl barbital (metharbital, Gemonil) and barbital in plasma. This method has been used to study the course of the conversion of N-methyl barbital to barbital and the course of the elimination of barbital.

Following intravenous injection of N-methyl barbital in the dog, barbital appears in the plasma, its concentration increasing as that of the unchanged drug decreases. The process of demethylation is slow, being only about half completed after 24 hr.

The conversion of N-methyl barbital to barbital by the dog is nearly complete.

Daily oral administration of N-methyl barbital to the dog results in accumulation of barbital in higher concentrations than those of the unchanged drug.

The possible role of barbital in therapeutic effects resulting from administration of N-methyl barbital is discussed.