10.4 Pediatric Pharmacology
Pediatric pharmacology addresses age-related differences in drug disposition and response, requiring specialized dosing and safety considerations.
Developmental Pharmacokinetic Changes
Absorption
- • ↑ Gastric pH (neonates) → ↑ absorption of weak bases
- • ↓ GI motility (neonates) → delayed absorption
- • Thinner skin → ↑ topical absorption
Distribution
- • ↑ Total body water (neonates 75-80% vs adult 60%)
- • ↓ Body fat → ↑ Vd for water-soluble drugs
- • ↓ Plasma protein binding → ↑ free drug
- • Immature BBB → ↑ CNS penetration
Metabolism
- • Immature hepatic enzymes (CYP450, glucuronidation)
- • Phase II matures slower than Phase I
- • Neonates: ↓ clearance of many drugs
- • Adolescents: ↑ clearance (may need adult doses)
Excretion
- • ↓ GFR (neonates ~30-40% of adult)
- • Adult GFR reached by 6-12 months
- • Dosing adjustments needed for renally cleared drugs
Dosing Strategies
Weight-Based Dosing
- • Most common: mg/kg
- • More accurate than age-based
- • May overdose obese children (use ideal body weight)
- • Example: Amoxicillin 20-40 mg/kg/day
Body Surface Area (BSA)
- • Used for chemotherapy, some critical drugs
- • More accurate for wide weight ranges
- • BSA (m²) = √[(height(cm) × weight(kg))/3600]
- • Example: Chemotherapy dosing
Drug Safety Concerns in Pediatrics
⚠️ Contraindicated/Caution Drugs
- Aspirin (age <16):
- • Reye syndrome risk (viral illness)
- • Hepatic encephalopathy, fatty liver
- Tetracyclines (age <8):
- • Permanent tooth discoloration
- • Inhibit bone growth
- Fluoroquinolones:
- • Cartilage damage in growing children
- • Use only if no alternative
- Codeine:
- • CYP2D6 ultra-rapid metabolizers → morphine toxicity
- • FDA warning for post-tonsillectomy pain
- Valproate:
- • Hepatotoxicity (age <2)
- • Fatal hepatic failure risk
- Benzyl alcohol:
- • Gasping syndrome in neonates
- • Found in some preservatives