Ontogeny of Human Conjugating Enzymes

Understanding the detailed ontogeny of xenobiotic metabolizing enzymes is important if we are to be able to predict the risk of toxicity to the developing fetus or the fate of drugs in neonates and children. This review summarizes current knowledge of the development of the major families of conjugating enzymes in humans: the UDP-glucuronosyltransferases, sulfotransferases, glutathione S-transferases, arylamine N-acetyltransferases and methyltransferases; little is known of the last three. Based on the available information, sulfation appears to be the most highly developed pathway during fetal development where glucuronidation in particular is lacking. Following birth, glucuronidation capacity develops rapidly and for many of the enzymes adult capacity occurs in mid-late childhood. The importance of developing pharmacokinetic and physiology-based pharmacokinetic models to support the more informed use of drugs in children is highlighted.