Indomethacin metabolism in isolated neonatal and fetal rabbit hepatocytes

Metabolism of indomethacin was examined in freshly isolated hepatocytes prepared by liver collagenase perfusion of fetal (28) and neonatal rabbits of 3, 5, 10, 12, and 25 days of age. Initial cell viability was more than 90% and linear rates of metabolism were observed for up to 2 hr of incubation. Deacylation of indomethacin to desbenzoyl indomethacin showed a rapid increase early in postnatal development while microsomal O-demethylation to desmethyl indomethacin was increased significantly only in the hepatocytes from 25-day-old rabbits. Glucuronide conjugates of indomethacin and indomethacin metabolites accounted for less than 8% of the total metabolites in hepatocytes from 25-day-old rabbits. The maturational development of indomethacin in metabolism may account for previously reported gestational dependent half-life of the drug in the premature infant (9). However, the factors that regulate development of indomethacin metabolism appear to be under more that one control system.