Aranda J V, MacLeod S M, Renton K W, Eade N R
J Pediatr. 1974 Oct;85(4):534-42. doi: 10.1016/s0022-3476(74)80465-8.
Many drugs require oxidative metabolism for termination of action and/or 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 analine 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 increasing 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.
许多药物需要通过氧化代谢来终止作用和/或从体内消除。许多氧化反应由肝脏微粒体酶催化。在从7名新生儿和4名成年患者获取的肝脏微粒体中,测定了各种药物代谢酶的活性,即NADPH细胞色素c还原酶、NADPH氧化酶、氨基比林-N-脱甲基酶和苯胺P-羟化酶,以及细胞色素P-450的含量。新生儿的结果显示,这些酶(氨基比林-N-脱甲基酶除外)的活性随年龄增长而增加。肝脏微粒体混合功能氧化酶系统的三个组分与苯胺p-羟化酶之间建立了良好的相关性,而只有NADPH氧化与氨基比林N-脱甲基化相关。底物或药物的氧化速率以及微粒体电子传递途径组分的活性低于成年人的相应值。这些数据证明了新生儿药物代谢短暂缺乏的可能生化基础。