Diazepam metabolism and anticonvulsant activity in newborn animals

Diazepam metabolism was studied in vivo and in vitro in newborn and adult rats and guinea-pigs. Both newborn rats and guinea-pigs are more sensitive to the antimetrazol action of diazepam than the adult animals. The difference in activity was about fifteen times for rats but only twice for guinea-pigs. This difference may be explained partly by the different levels of diazepam and its metabolites in the brain of newborn and adult animals. The total benzodiazepines present in the brain of newborn rats and guinea-pigs were always higher than in adult animals. Studies carried out with liver microsomal enzymes indicate that the metabolism in newborn animals is considerably reduced in respect to adult rats and guinea-pigs.