Pathophysiology
Clinical meaning
Pediatric pharmacokinetics differ from adults across all ADME parameters. Absorption is affected by higher gastric pH in neonates (achlorhydria until 2-3 months), slower gastric emptying, and variable first-pass metabolism. Distribution differs due to higher total body water (70-80% in neonates vs 55-60% in adults), lower protein binding (decreased albumin and alpha-1-acid glycoprotein), and an immature blood-brain barrier allowing greater CNS drug penetration. Hepatic metabolism matures at different rates for each CYP enzyme: CYP3A7 predominates in neonates and transitions to CYP3A4 by 6-12 months, while CYP2D6 reaches adult activity by 3-5 years. Renal elimination is reduced in neonates (GFR 2-4 mL/min at birth, reaching adult values by 1-2 years), requiring dose adjustments for renally cleared drugs.