Maturational pharmacokinetics of single intravenous bolus of propofol

Paediatr Anaesth. 2007 Nov;17(11):1028-34. doi: 10.1111/j.1460-9592.2007.02285.x.

Abstract

Background: Our aim was to document propofol pharmacokinetics in preterm and term neonates following a single intravenous bolus and compare these estimates with pharmacokinetics findings in toddlers and young children.

Methods: Newly collected observations following intravenous bolus administration of propofol in preterm and term neonates (n = 9) were compared with earlier reported pharmacokinetic estimates in toddlers and young children. Data are reported by median and range. Mann-Whitney U-test or correlation was used to analyze differences in pharmacokinetic findings between neonates, toddlers and young children.

Results: Concentration-time profiles obtained were interpreted by two-stage analysis as a three compartment open model in nine neonates with a median weight of 2.51 (range 0.91-3.8) kg and a median postmenstrual age (PMA) of 36 (range 27-43) weeks. Median clearance (CL) was 13.6 (range 3.7-78.2) ml.min(-1).kg(-1) and median apparent volume of distribution at steady state (V(ss)) was 3.7 (1.33-7.96) l.kg(-1). Following allometric scaling and standardization to 70 kg, median CL was 442 (range 97-2184) ml.min(-1).70 kg(-1). Compared with earlier reported observations in toddlers and children, median clearance (kg.min(-1)) was significantly lower in neonates (P < 0.01) and these differences remained significant after allometric scaling (70 kg.min(-1)) while V(ss) (l.kg(-1)) was significantly lower in neonates (P < 0.01).

Conclusions: 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, a longer recovery time is more likely to occur in neonates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Anesthetics, Intravenous / administration & dosage
  • Anesthetics, Intravenous / blood
  • Anesthetics, Intravenous / pharmacokinetics*
  • Body Weight / physiology
  • Humans
  • Infant, Newborn
  • Infusions, Intravenous
  • Metabolic Clearance Rate / physiology
  • Propofol / administration & dosage
  • Propofol / blood
  • Propofol / pharmacokinetics*
  • Statistics, Nonparametric

Substances

  • Anesthetics, Intravenous
  • Propofol