Abstract

Pretreatment of both newborn and fetal rabbits, by injection of the pregnant doe with phenobarbital sodium or by injection of the new-born from untreated does, resulted in significant increases in drug enzyme activity by livers from these fetal and newborn animals. These increases were not seen in livers from fetuses taken 4 or 8 days prior to term from pretreated does.

Concurrent treatment with DL-ethionine, an amino acid antagonist, blocked these increases in enzyme activity. This finding suggests synthesis of the drug metabolizing enzymes might be the mechanism of phenobarbital stimulation, although several other mechanisms are still possible and are mentioned.

It was also pointed out that the adult rabbit, unlike the rat, has hepatic drug metabolizing enzymes which can be markedly stimulated by phenobarbital. This may make the rabbit more desirable than the rat for study of this phenomenon.