Summary of ontogenic patterns of CYP isoforms and their potential clinical impact
| CYP isoform | Observed ontogenic pattern | Examples of substrate drug(s) used in children | Potential clinical impact |
|---|---|---|---|
| CYP1A2 | Absent or significantly low levels at birth as compared with the levels detected in the later age groups | Caffeine (Buck, 1997) | Lower metabolic clearance in neonates |
| CYP2B6 | Consistent levels across all age groups until adulthood | Cyclophosphamide (Buck, 1997) | No changes in clearance across ages |
| CYP2C8 | Absent or significantly low levels at birth as compared with the levels detected in the later age groups | Paclitaxel (Buck, 1997) | Significantly lower metabolic clearance in neonates as compared with later age groups |
| CYP2C9 | Low levels at birth that significantly increase after birth to reach adult levels | Warfarin, tolbutamide (Buck, 1997) | Lower metabolic clearance at birth, which increases to adult levels in 26-day to 1-year age group |
| CYP2C19 | Absent or significantly low levels at birth as compared with the levels detected in the later groups | Omeprazole, pantoprazole (Buck, 1997) | Lower metabolic clearance in neonates |
| CYP2D6 | Lower levels in the 0- to 12-day age group, followed by a 2- to 3-fold increase in 26 days to 1 years with no significant change in the later age groups | Dextromethorphan, codeine (Buck, 1997) | Lower metabolic clearance at birth, which increases to adult levels in 26-day to 1-year age group |
| CYP2E1 | An increase of ∼ninefold in from the 0-12 d to reach adult levels by 26 d-1 yr age group | Chloroxazone (Buck, 1997) | Lower metabolic clearance at birth, which increases to adult levels in 26-day to 1-year age group |
| CYP3A4 | Not detected in the neonatal samples, replaces CYP3A7 as the major CYP3A isoform in the later age groups | Midazolam, clindamycin (Buck, 1997) | Markedly decreased metabolic clearance in neonates with an increasing trend with age |
| CYP3A5 | Consistent levels across all age groups till adulthood | Cyclophosphamide, tamoxifen (also metabolized by CYP3A4) (Buck, 1997) | No significant changes in clearance across ages |
| CYP3A7 | Most abundant drug-metabolizing enzyme in 0- to 12-day age group, with a sharp decline and switch to CYP3A4 in the later age groups | Endogenous compounds like dehydroepiandrosterone, environmental pollutants like aflatoxin B1 (Hashimoto et al., 1995; Lacroix et al., 1997; Ohmori et al., 1998) | Protecting fetus from environmental toxins, with switch to CYP3A4 for metabolism of exogenous compounds in the later age groups |
| CYP4F2 | Lowest expression at 0 to 12 days followed by an increase in the later age groups | Vitamin K, warfarin, fingolimod (McDonald et al., 2009; Piri Cinar et al., 2023) | Lower metabolic clearance in neonates |
| CYP4F3 | Consistent levels across all age groups until adulthood | Fingolimod (Piri Cinar et al., 2023) | No significant changes in clearance across ages |
| CYP4F11 | Lowest expression at 0-12 d followed by an increase in later age groups | Vitamin K, erythromycin and chlorpromazine (Ginsburg and Eichenwald, 1976) | Lower metabolic clearance in neonates |
| CYP4F12 | Highest expression 26 days to 1 year, followed by a decline in later age groups | Ebastine (Estelle et al., 1993) | Higher metabolic clearance in 26 days to 1 year, with decline in later age groups |