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Pharmacokinetic-pharmacodynamic modeling of propofol in children

Agnes Rigouzzo1, Frederique Servin, Isabelle Constant

  • 1Department of Anesthesiology, Armand Trousseau Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), University Pierre et Marie Curie, Paris, France.

Anesthesiology
|July 9, 2010
PubMed

Insights

The Schnider model best described propofol pharmacokinetics in children, outperforming pediatric models. This suggests its utility for target-controlled infusions in pediatric anesthesia.

Area of Science:

  • Anesthesiology
  • Pharmacokinetics
  • Pharmacodynamics

Background:

  • Optimizing anesthetic drug delivery in pediatric patients requires accurate pharmacokinetic and pharmacodynamic models.
  • Current pediatric models may not fully capture the complexities of drug behavior in prepubertal children.

Purpose of the Study:

  • To identify the optimal model for describing propofol pharmacokinetics and pharmacodynamics in prepubertal children.
  • To calculate relevant pharmacodynamic parameters for pediatric anesthesia.
  • To validate the chosen model by including postpubertal subjects.

Main Methods:

  • Compared four pharmacokinetic models (Kataria, pediatric Marsh, Schüttler, Schnider) for propofol in 16 children (6-12 years) and 13 adults (13-35 years).
  • Utilized plasma target-controlled infusion based on established models for induction.
  • Analyzed bispectral index (BIS) in relation to predicted propofol concentrations.

Main Results:

  • The Schnider model demonstrated the best performance in describing the concentration-effect relationship in children.
  • Pooling data revealed puberty as a significant covariate influencing key parameters like kE0 (effect-site equilibration rate constant) and Ce50 (median effect-site concentration for 50% maximal effect).
  • Children exhibited shorter time-to-peak effect and higher Ce50 values compared to adults.

Conclusions:

  • The Schnider model, typically used for adults, proved superior to existing pediatric models for predicting propofol effects in children.
  • This study supports the potential use of the Schnider model for propofol target-controlled infusion in pediatric anesthesia.
  • Puberty significantly influences propofol's pharmacodynamic parameters, necessitating model adjustments for different age groups.
Abstract

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