Development of narcotic drug metabolizing enzymes in the newborn rat

Liver 9000 x g supernatant of rats from 1 day of age to adult was used as the enzyme source to study glucuronidation of morphine, O-demethylation of norcodeine and N-demtheylation and ester hydrolysis of meperidine. Uridine diphosphate glucuronyl transferase activity in 1-day-old rats was about one-fifth of that of the adult, increased to the adult level between 3 and 7 days of age and exceeded that of the adult when the rats were 28 days old. The activities of O- and N-demethylase were first observed in the liver of 3- and 7-day-old rats, respectively, and increased to the adult level at 35 days of age. Esterase activity was first observed in 14-day-old rats and increased rapidly to the adult level at 35 days of age. Drug metabolizing capacity for newborn rats, in terms of percentage of that of adults (calculated based on the specific enzyme activity, protein content of the liver and liver weight), was quite low for the first 2 weeks of life, ranging from undetectable to less than 5% of the adult level. The capacity increased during the next 3 weeks, reaching about 50 to 75% of adult activities by the 35th day.