The development of hepatic drug-metabolizing enzyme activity in the neonatal calf and its effect on drug disposition

Mixed function oxidase and UDP-glucuronyltransferase activity was measured in liver microsomal preparations from 1-, 7-, and 42-day-old, male, Holstein calves. Liver samples were obtained by a surgical biopsy procedure that allowed for multiple samples to be taken from a single individual. Microsomal protein content doubled between 7 and 42 days of age and reached adult levels during this time. Cytochrome P-450 content increased 2-fold during the first week and remained constant thereafter. NADPH-cytochrome c reductase activity doubled during the first week, but then returned to its initial level by 42 days of age. UDP-glucuronyltransferase activity was well developed at 1 day of age and reached adult levels by 7 days of age. Mixed function oxidase activity was less well developed; activities at 1 day of age were only 17-50% of those at 42 days of age for O-deethylation, O- and N-demethylation, and aryl hydrocarbon hydroxylation. Development of hepatic drug-metabolizing activity was discussed in relation to the age-related increase in the rate of elimination of the antibacterial compound trimethoprim.