Hepatic microsomal drug oxidation and electron transport in newborn infants

Many drugs requine oxidative metabolism for termination of action andlor for elimination from the body. Many oxidative reactions are catalyzed by hepatic microsomal enzymes. The activities of various drug-metabolizing enzymes, namely, NADPH cytochrome c reductase, NADPH oxidase, aminopyrine-N-demethylase, and aniline p-hydroxylase, and the content of cytochrome P-450, were measured in hepatic microsomes obtained from seven newborn infants and four adult patients. The results in the newborn infant show incrneasing activities of these enzymes (except aminopyrine-N-demethylase) related to advancing age. Good correlation between three components of the hepatic microsomal mixed function oxidase system and aniline p-hydroxylase was established, whereas only NADPH oxidation correlated with aminopyrine N-demethylation. The rate of substrate or drug oxidation and the activities of the components of the microsomal electron transport pathway were lower than comparable values in the adult. The data demonstrate a possible biochemical basis for the transient deficiency in drug metabolism seen in newborn infants.