Pathophysiology
Clinical meaning
Pediatric pharmacokinetics differ significantly from adults due to developmental changes in body composition and organ maturation. Neonates have higher total body water (75-80% vs 55-60% in adults), increasing the volume of distribution for hydrophilic drugs (aminoglycosides, vancomycin require higher mg/kg doses). Lower protein binding (reduced albumin and alpha-1 acid glycoprotein) increases free drug fraction. Hepatic drug metabolism develops at different rates: phase I reactions (CYP450 oxidation) mature by 6 months to 2 years, while phase II conjugation (glucuronidation) matures by 3-4 years (chloramphenicol toxicity in neonates from immature glucuronidation = gray baby syndrome). Renal glomerular filtration rate reaches adult values by 6-12 months but is only 25-30% of adult GFR at birth. Drug dosing errors are the most common and preventable adverse events in pediatrics, with 10-fold dosing errors being particularly lethal. The Broselow tape estimates weight-based dosing from length in emergency situations.