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Human physiologically based pharmacokinetic model for propofol.

David G Levitt1, Thomas W Schnider

  • 1Department of Physiology, University of Minnesota, 6–125 Jackson Hall, 321 Church St, S, E,, Minneapolis, MN 55455, USA. levit001@umn.edu.

BMC Anesthesiology
|April 26, 2005
PubMed
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This study introduces the first detailed human physiologically based pharmacokinetic (PBPK) model for propofol, accurately describing its complex kinetics. The PBPK model offers advantages for predicting pharmacokinetic changes in various patient populations.

Area of Science:

  • Pharmacokinetics
  • Pharmacology
  • Physiology

Background:

  • Propofol is a widely used anesthetic with complex pharmacokinetics due to high lipid solubility.
  • Traditional pharmacokinetic descriptions rely on multi-compartmental models.
  • Physiologically based pharmacokinetic (PBPK) modeling offers a more mechanistic approach.

Purpose of the Study:

  • To develop and validate the first detailed human physiologically based pharmacokinetic (PBPK) model for propofol.
  • To assess the model's ability to describe propofol kinetics across various dosages, ages, and body compositions.
  • To evaluate the PBPK model's predictive capabilities for altered physiological states.

Main Methods:

  • Utilized PKQuest software for calculations.
  • Employed standard human PBPK parameters and determined propofol oil/water partition coefficient and lipid fractions.

Related Experiment Videos

  • Fitted the PBPK model to experimental data involving a propofol bolus dose followed by a constant infusion.

    • Main Results:

    • The PBPK model accurately described experimental data across a range of dosages, ages, and fat fractions.
    • Only liver clearance required adjustment for the infusion phase.
    • Lung sequestration was necessary for 10 of 24 subjects to fit the bolus injection phase.
    • Achieved an average weighted residual error (WRE) of 15% for both bolus and infusion phases.

    Conclusions:

    • A PBPK model with standard human parameters and simple tissue binding effectively describes human propofol kinetics.
    • PBPK models are advantageous for predicting pharmacokinetic changes due to physiological variations.
    • The model shows potential for simulating pharmacokinetic alterations in conditions like morbid obesity.