Pediatric Pharmacology

Pediatric Pharmacology

1. Definition, scope & the central principle

• Paediatric pharmacology is the study of how drugs are handled by, and act upon, the developing human from birth through adolescence — a continuum in which absorption, distribution, metabolism, excretion (ADME) and pharmacodynamic responsiveness change with age rather than remaining fixed. (KDT 8e Ch.5, p.73)
• The cardinal axiom: "infants and children are not small adults." They have important physiological differences from adults, so paediatric doses and dosing intervals must be learned as such and not derived from any formula scaled down from the adult dose. (KDT 8e Ch.5, p.74)
  • This stands in deliberate contrast to the older practice of computing a child's dose by applying an age- or weight-based fraction to the adult dose; KDT explicitly states the age-based formulae "are not in use now." (KDT 8e Ch.5, p.74)
• Two intertwined reasons make paediatrics a distinct discipline rather than a dose-scaling exercise: (a) developmental pharmacokinetics — organ systems that clear drugs (kidney, liver) mature postnatally on their own timetable; and (b) developmental vulnerabilities — immature handling exposes specific organs (brain, marrow, growing bone/teeth/epiphyses) to drug toxicities not seen in adults. (KDT 8e Ch.5, p.74; KDT 8e Ch.6, p.96)
• The neonate and premature infant are the extreme of this spectrum: defects of immature elimination "are exaggerated in the premature infant." (KDT 8e Ch.5, p.74)

1.1 — Why dose-individualization is mandatory in children

• Recommended adult doses are "based on population data and cater to an 'average' patient," but individual patients deviate in pharmacokinetic and pharmacodynamic parameters — a deviation that is maximal in the very young, mandating individualization. (KDT 8e Ch.5, p.73)
• Dosing strategy in children inherits the general framework: standard dose (wide safety margin), regulated dose (titrate to a measurable physiological endpoint), target-level dose (aim for a plasma concentration, then adjust by therapeutic drug monitoring [TDM]), and titrated dose (raise until limited by adverse effect). For narrow-window drugs in neonates, the target-level/TDM strategy dominates because immature clearance makes the plasma level unpredictable from dose alone. (KDT 8e Ch.5, pp.73, 74)