Pathophysiology
Clinical meaning
Pediatric weight-based dosing compensates for age-related pharmacokinetic differences. Neonates have higher total body water (70-80%), lower serum albumin, immature hepatic CYP enzymes (CYP3A7 transitions to CYP3A4 by 6-12 months), and low GFR (2-4 mL/min at birth, adult values by 1-2 years). Toddlers and young children may have accelerated hepatic metabolism relative to body weight, sometimes requiring higher mg/kg doses than adults. Obese children present dosing challenges: hydrophilic drugs should be dosed on ideal body weight while lipophilic drugs use adjusted body weight. The therapeutic index must account for the fact that the 10x dosing error (decimal point misplacement) is the most dangerous and common pediatric medication error.