A review of developmental aspects of cytochrome P450.

Abstract

This article surveys the development of human hepatic P450 cytochromes (CYPs) involved in xenobiotic metabolism from the fetus through the life span and explores possible clinical consequences of developmental issues. These hepatic P450 CYPs come "on line" at different times during fetal and infant development, and each one is discussed in that temporal sequence. CYP3A7. the major fetal hepatic cytochrome, is present during organogenesis, and it is involved in steroid metabolism. Variably expressed in some fetuses, CYP3A5 is also present at significant levels in about half of all children. In adults, CYP3A4 is the major functional member of the CYP3A subfamily. CYP1A1 is also present during organogenesis, and it metabolizes exogenous toxins, some of which are procarcinogens. CYP2E1 may be present in some second-trimester fetuses, and it may be involved in prenatal alcohol metabolism. After birth, hepatic CYP2D6 and CYP2C8/9 and CYP2C18/19 become active. Both CYP2D6 and CYP2C19 have genetic polymorphisms that can bring about differing capacities to metabolize exogenous drugs, including psychotropic drugs. CYP1A2 becomes active in the fourth to fifth postfetal months. It provides the best current examples of the importance of developmental changes in xenobiotic-metabolizing P450 CYPs through its metabolism of caffeine and theophylline in premature infants, neonates, and adolescents.