Pre- and postnatal enzyme capacity for drug metabolite production

Abstract

Most lipid soluble foreign compounds including drugs, insecticides and many environmental pollutants are metabolized in animals by cytochrome P 450 enzymes in the endoplasmic reticulum of liver. These enzymes are virtually absent in fetuses of laboratory animals, but their activities increase to adult levels within 3-8 wk after birth. In human fetuses, the enzymes appear during the first half of pregnancy, and their activities during gestation reach about 1/3 of those found in adults. The species differences in fetal activities apparently parallel the differences in the development of liver endoplasmic reticulum. In laboratory animals, the rough surfaced reticulum does not develop until 4 days before birth and the smooth surfaced reticulum develops only after birth. In man, however, the rough surfaced form appears at about 7 to 9 wk of gestation, whereas the smooth surfaced form appears at about the 3rd mth of pregnancy. Despite the early development of these enzymes in humans, they probably play only a minor role in limiting the accumulation of most foreign compounds in human fetuses. Nevertheless, they may play an important role in drug induced toxicities, particularly those that are mediated through the formation of chemically reactive metabolites.