Phenobarbital metabolism in adults and in newborn infants.

Two adult volunteers and four newborn infants were given a single dose of phenobarbital. The output in the urine o f unchanged phenobartital and of the two main metabolites p-hydroxy phenobarbital and conjugated p-hydroxy phenobarbital was followed during 8 days in the newborns and during 2 or 4 weeks in the adults. The plasma levels were also determined and some pharmacokinetic constants calculated. It was found that the newborn patients excreted unchanged phenobartibal and p-hydroxy phenobarbital in the same proportions relative to dose as did the adult volunteers, 2.e. 16--17% unchanged drug and 9--10% of the metabolite during the first 8 days after administration. On the other hand, there was a clear-cut age difference in output of conjugated metabolite where the newborns excreted only 5% of the given dose during the 8-day observation period. The corresponding value for the adults was 15%. It is concluded that a poor conjugating capacity in the newborn may not have any serious consequences with a drug like phenobarbital where major alternative routes of excretion exist (unchanged drug and unconjugated metabolite). The clinical significance of immature drug metabolites and of unchanged drug is taken into consideration.