B SYL2017: Neonate PK changes

Absorption

PO Absorption

  • Prems @ 25 weeks have N-K-ATPase & produce gastric acid
  • pH at site influences extent of ionisation & absorption
  • Passive diffusion of small unionised molecules
  • ↓absorption with delayed gastric emptying (P stenosis, low gestational age)
  • ↑emptying = human milk, low cal feeds

Transdermal

  • Variable
  • ↑SA → ↑drug exposure (per kg cf. adults)

Rectal

  • Upper rectal v → 1st pass
  • Middle & inf → IVC

Distribution

↑↑↑Fluid & Overhydration

  • ∴↑VD polar drugs, requiring ↑dose

↓Muscle & Fat

  • Drugs which distribute to muscle & fat (Thio, F) will need ↓dose to avoid ↑Cp

↓PPB

  • Acidic + basic drugs = ↑free drug

Immature BBB

  • ↑sensitivity CNS effects of drugs

Metabolism

HBF

  • ↑as neonate matures
  • Drug clearance variable

Immature Enzyme Systems

  • Markedly ↓P450 enzyme activity
  • ↓plasma cholinesterase
  • ∴variable & incomplete drug metabolism

Elimination

  • ↓excretion of drugs renally
  • Crt Cl < 10% of adult
  • Glomerular & tubule function mature by 2 years
  • Drugs with 1° renal elimination will have vastly prolonged t ½b (aminoglycosides, cephalosporins)