title: Pharmacokinetics - Neonatal Intensive Care Drug Manual
text: Pharmacokinetics:
  Propofol (2,6-diisopropylphenol) is a highly lipophilic anaesthetic that is metabolised in the liver. Subsequently, its metabolites are eliminated by the renal route. Its clearance mainly depends upon the hepatic blood flow with subsequent glucuronidation or hydroxylation in adults. Propofol disposition is best described by a 3-compartment model, with a rapidly equilibrating central compartment, a second larger peripheral compartment and a third, very large peripheral compartment. Children demonstrate increased clearance and larger volumes of distribution relative to adults, consequently require higher induction and maintenance doses.[10] However, markedly reduced clearance has been reported in neonates.[11, 12] Allegaert et al 2007 [12] reported pharmacokinetics in preterm and neonates after IV bolus administration of propofol 3 mg/kg over 10 seconds. Propofol clearance at 38 weeks PMA was 0.029 L/min. Postmenstrual age (PMA) and postnatal age (PNA) contribute to the inter-individual variability of propofol clearance with very fast maturation of clearance in neonatal life. The addition of a fixed value in neonates with a PNA of ≥10 days resulted in the equation for CL = CL(std).(PMA/38)(11.5) + 0.03] for neonates ≥10 days. Extensive inter-individual variability in propofol clearance (range: 3.7–78.2 ml/kg/min) within the neonatal population has also been reported.[13] Propofol clearance was reduced (typically by 26%) in children who had undergone cardiac surgery.[14]
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