Table 1.
Developmental expression of drug-metabolizing enzymes in the neonate
| Enzyme (ref) | Example Drugs | Enzyme Ontogeny |
|---|---|---|
| CYP1A1/2 (2, 13, 30, 32, 35) | caffeine | absent-to-low expression in the neonate; activity reaches 50% of adult values by 1 year of age; formula-fed infants have faster maturation |
| CYP2C19 (24, 30) | phenobarbital, phenytoin, diazepam | low expression from birth to 2 days of age with a rapid increase over 1 week of age; adult levels reached by 2 years of age |
| CYP2C9 (2, 13, 15, 30) | phenobarbital, indomethacin, ibuprofen, phenytoin | low activity through 2–4 weeks of age; adult activity achieved by 1–6 months of age; activity exceeds adult levels by 3–10 years and returns to adult levels by puberty |
| CYP2D6 (13, 15, 30) | antiarrhythmic, beta-antagonists, | absent until 7 days of life and reaches 20% of adult levels at 1 month of age; adult activity achieved by 3–5 years of age |
| CYP2E1 (30, 33) | acetaminophen | approximately 10% of adult activity in the newborn period; steadily increases to 30% by 3–12 months of age; reaches adult levels between 1–10 years of age |
| CYP3A4 (13, 15, 30, 32, 35, 36) | dexamethasone, diazepam, erythromycin, fentanyl, methadone, midazolam, nifedipine, sildenafil | low expression at birth; increases to 30% adult levels by 1 month of age; almost 5-fold increase by 3 months of age; full adult activity reached by 6 months of age; formula-fed infants may have faster maturation |
| CYP3A7 (15, 31, 32) | retinoic acid | dominantly expressed enzyme in the CYP3A subfamily during the fetal period; activity begins to decrease after birth; disappears by 1–4 weeks of age |
| FMO1 (30, 31, 37) | voriconazole, ranitidine | highest levels during fetal period; suppression of expression can begin within days after birth; decrease in activity is not linked with increase in FMO3; there may be a period with little FMO activity |
| FMO3 (30, 37) | voriconazole, ranitidine | low or undetectable levels in neonates; detectable activity may not occur until 1–2 years of age |
| UGT2B7 (24, 33) | morphine | present in fetal liver at 10–20% of adult levels; expression increases after birth; adult levels by 2–3 months of age |