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)