Development of the Hepatic Mixed-Function Oxidase System and Its Metabolism of Warfarin in the Perinatal Rat

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Abstract
The development of the rat hepatic microsomal mixed-function oxidase system was investigated by analyzing its components in fetal and young pups of postconceptional age 18-54 days. Cytochrome P-450 and cytochrome b5 concentrations and NADPH-cytochrome c reductase and R-warfarin hydroxylase activities were determined as a function of postconceptional age. The cytochromes and reductase were present and increased with age before birth, and major increases were detected in the first 2 days after birth. The cytochrome P-450 concentration increased again markedly at puberty, whereas reductase activity increased before puberty and reached the adult level at puberty. Metabolism of warfarin to specific metabolites indicated that at 37 days postconception the isozyme cytochrome P-450 UT-C began to predominate. Its domination of the hepatic cytochrome P-450 pool increased with age.