Inter-individual Variability in Propofol Pharmacokinetics in Preterm and Term Neonates

TLDR: PMA and PNA contribute to the inter-individual variability of propofol clearance with very fast maturation of clearance in neonatal life and implicates that preterm neonates and neonates in the first week of postnatal life are at an increased risk for accumulation during either intermittent bolus or continuous administration of prop ofol.

Abstract: Background To document covariates which contribute to inter-individual variability in propofol pharmacokinetics in preterm and term neonates. Methods Population pharmacokinetics were estimated (non-linear mixed effect modelling) based on the arterial blood samples collected in (pre)term neonates after i.v. bolus administration of propofol (3 mg kg−1, 10 s). Covariate analysis included postmenstrual age (PMA), postnatal age (PNA), gestational age, weight, and serum creatinine. Results Two hundred and thirty-five arterial concentration–time points were collected in 25 neonates. Median weight was 2930 (range 680–4030) g, PMA 38 (27–43) weeks, and PNA 8 (1–25) days. In a three-compartment model, PMA was the most predictive covariate for clearance (P 0.001). Conclusions PMA and PNA contribute to the inter-individual variability of propofol clearance with very fast maturation of clearance in neonatal life. This implicates that preterm neonates and neonates in the first week of postnatal life are at an increased risk for accumulation during either intermittent bolus or continuous administration of propofol.