General Pediatric Pharmacotherapy Principles, Growth, and Development
Anchors for dosing
Pediatric dosing rests on three anchors: fixed mg/kg, body surface area, and age/weight algorithms. BSA (Mosteller: square root of [height cm × weight kg ÷ 3600]) is preferred for narrow-therapeutic-index agents (chemotherapy, some immunosuppressants, antifungals) because it tracks GFR and metabolic rate. Always cap a mg/kg dose at the adult maximum.
Developmental physiology drives the traps
Neonates hold 70–80% total body water, so hydrophilic drugs (aminoglycosides, beta-lactams) have a larger volume of distribution and need higher mg/kg doses, while lipophilic drugs distribute less. Albumin and alpha-1-acid glycoprotein are low, raising the free fraction of highly bound drugs such as phenytoin and ceftriaxone (which also competes with bilirubin). GFR is roughly 30–40% of adult at term and matures by 6–12 months, so renally cleared drugs need prolonged intervals early in life. Hepatic pathways mature on a schedule (CYP3A7 gives way to CYP3A4; glucuronidation lags for 2–3 months), and gastric pH is higher with delayed emptying, changing absorption of weak acids and enteric-coated dosage forms.
Age-related contraindications
Frequently tested: tetracyclines under 8 years (dental staining; short-course doxycycline is an exception for rickettsial disease), aspirin during viral illness (Reye syndrome), codeine and tramadol under 12 years (CYP2D6 ultrarapid metabolism), valproate under 2 years (hepatotoxicity), ceftriaxone in hyperbilirubinemic neonates or with calcium-containing fluids, promethazine under 2 years, and benzyl alcohol–preserved products in neonates.
Worked example
A 12 kg 2-year-old needs amoxicillin 90 mg/kg/day divided twice daily. 90 × 12 = 1080 mg/day; 540 mg per dose. With 400 mg/5 mL suspension, that is 6.75 mL twice daily. Note the total daily dose is far above a typical adult 500 mg capsule - the mg/kg cap, not intuition, governs.