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Related Experiment Videos

Using front-end kinetics to optimize target-controlled drug infusions.

Michael J Avram1, Tom C Krejcie

  • 1Department of Anesthesiology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Ward 13-199, Chicago, Illinois 60611-3008, USA. mja190@northwestern.edu

Anesthesiology
|October 25, 2003
PubMed
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Accurate pharmacokinetic models are crucial for target-controlled infusion (TCI). Models based on early arterial drug concentrations lead to overshooting the target, while fixing initial distribution volume (VC) ensures minimal deviation for effective TCI design.

Area of Science:

  • Pharmacokinetics
  • Pharmacodynamics
  • Drug Infusion Systems

Background:

  • Drug administration routes, sampling times, and sites influence pharmacokinetic models.
  • This study investigates if pharmacokinetic model parameters from rapid intravenous thiopental administration can design accurate target-controlled infusions (TCI).

Purpose of the Study:

  • To test if three-compartment pharmacokinetic model parameters from arterial concentrations after rapid IV administration can create a TCI with minimal deviation from the target.
  • To evaluate the accuracy of TCIs designed using different pharmacokinetic models.

Main Methods:

  • Utilized arterial thiopental concentration data from a previous canine study.
  • Constructed three-compartment models using early concentrations, all concentrations post-recirculation peak, and a fixed initial distribution volume (VC).

Related Experiment Videos

  • Designed and simulated TCIs to maintain a target concentration, evaluating prediction errors against recirculatory model kinetics.

    • Main Results:

    • Models using early or frequent concentrations overestimated VC and tissue volumes, leading to TCI overshoot.
    • Fixing VC to recirculatory model parameters resulted in accurate drug distribution and minimal TCI deviation.
    • A comparable three-compartment model was derived from a simulated 2-minute infusion using recirculatory kinetics.

    Conclusions:

    • Three-compartment models based on rapid IV administration data inaccurately characterize VC, causing TCIs to exceed target concentrations.
    • A model derived from data during and after a brief infusion can produce TCIs with minimal deviation from the target.