Perspectives in Pharmacology The Ontogeny of Human Drug-Metabolizing Enzymes: Phase I

Although some patterns are beginning to emerge, our knowl-edge of human phase I drug-metabolizing enzyme develop-mental expression remains far from complete. Expression has been observed as early as organogenesis, but this appears restricted to a few enzymes. At least two of the enzyme families that are expressed in the fetal liver exhibit a temporal switch in the immediate perinatal period (e.g., CYP3A7 to CYP3A4/3A5 and FMO1 to FMO3), whereas others show a progressive change in isoform expression through gestation (e.g., the class I alcohol dehydrogenases). Many of the phase I drug-metabo-lizing enzyme exhibit dynamic perinatal expression changes that are regulated primarily by mechanisms linked to birth and secondarily to maturity. A few of these enzymes are not detect-able until well after birth, suggesting that birth is necessary bu