Pharmacokinetics of single intravenous bolus administration of propofol in preterm and term neonates

Background

The aim of this study is to describe maturational aspects of propofol pharmacokinetics following single intravenous bolus administration in childhood.

Methods

Seventy propofol blood–time profiles were collected in nine neonates (mean weight 2.4, range 0.91–3.8 kg) by arterial blood samples up to 24 hours after administration of a single intravenous bolus of propofol (3 mg/kg over 10 s) before elective chest tube removal. Concentration–time curves obtained for every individual neonate were interpreted by two-stage analysis as two-compartment and three-compartment open models. These newly collected observations following intravenous bolus administration of propofol in preterm and term neonates (n = 9) were combined with individual pharmacokinetic estimates in toddlers (n = 12) and young children (n = 10) [1, 2]. Data were reported by the median and range. The Wilcoxon test or linear correlation were used to analyse the pharmacokinetic findings in neonates, toddlers and young children.

Results

The blood–concentration curves obtained for every individual patient were interpreted by two-stage analysis as a three-compartment open model in a cohort of 31 patients with a median weight of 11.2 (range 0.91–24) kg and a median postmenstrual age of 108 (range 27–405) weeks. The median clearance was 36.8 (range 3.7–78.1) ml/kg/min, the median apparent volume of distribution at steady state (V_ss) was 7.6 (1.33–15.6) l/kg and the median final serum elimination half-life was 377 (range 27–1134) minutes. Median clearance was significantly lower in neonates compared with toddlers and older children (P < 0.01) and these differences remained significant after allometric scaling (ml/kg 0.75/min). A significant correlation between V_ss and postmenstrual age (r = 0.61, 95% CI 0.32–0.8, P < 0.004) was observed.

Conclusion

Propofol disposition is significantly different in neonates compared with toddlers and young children, reflecting both ontogeny and differences in body composition. Based on the reduced clearance of propofol, accumulation during repeated administration and longer recovery time are more likely to occur in neonates.