QUANTITATIVE STUDIES OF THE METABOLIC FATE OF MEPHOBARBITAL (N-METHYL PHENOBARBITAL)

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

An ultraviolet spectrophotometric method is described for the simultaneous determination of mephobarbital and phenobarbital in plasma. This method has been used to study the course of demethylation of mephobarbital and other aspects of its physiological disposition.

After an intravenous injection of mephobarbital in the dog, the gradual disappearance of the unchanged drug from the plasma is accompanied by a corresponding increase in concentration of the product of demethylation, phenobarbital. Although the demethylation requires many hours for completion, it is a rapid process relative to the elimination of phenobarbital. Phenobarbital is detectable in the plasma for several days after mephobarbital has disappeared.

Mephobarbital is almost completely converted to phenobarbital by the dog. Very little of the unchanged drug is excreted.

Oral doses of mephobarbital are incompletely absorbed by the dog.

Chronic oral administration of mephobarbital to the dog leads to accumulation of phenobarbital but not of the unchanged drug.

In human patients receiving mephobarbital by mouth the plasma concentration of phenobarbital is much higher than that of unchanged mephobarbital.

The role played by phenobarbital in the pharmacological effects resulting from administration of mephobarbital is discussed.