Population pharmacokinetics of propofol: a multicenter study

Area of Science:

• Pharmacology
• Anesthesiology
• Pharmacokinetics

Background:

• Target-controlled infusion (TCI) of propofol is increasingly common.
• Accurate pharmacokinetic models are essential for TCI, especially considering patient factors like age and weight.
• A multicenter population analysis was conducted to quantify covariate effects on propofol pharmacokinetics.

Purpose of the Study:

• To develop a population pharmacokinetic model for propofol.
• To investigate the influence of covariates such as age and weight on propofol pharmacokinetics.
• To improve the precision of target-controlled infusion systems.

Main Methods:

• Analysis of 4,112 samples from 270 individuals (age 2-88 years, weight 12-100 kg).
• Population pharmacokinetic modeling using NONMEM software.
• Estimation of inter- and intraindividual variability for clearances and volumes, investigating effects of age, weight, administration type, and sampling site.

Main Results:

• A three-compartment model best described propofol pharmacokinetics.
• Weight significantly impacted elimination clearance, intercompartmental clearances, and compartment volumes (power functions with exponents < 1).
• Age influenced elimination clearance (linear decrease > 60 years) and central compartment volume; pediatric parameters increased when normalized to body weight. Administration route and sampling site also affected parameters.

Conclusions:

• A three-compartment model adequately describes propofol pharmacokinetics.
• Incorporating age and weight as covariates significantly enhances the pharmacokinetic model.
• Individualized pharmacokinetic adjustments via covariate inclusion can improve TCI precision and potentially expand its clinical applications.