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A novel technique to determine an 'apparent ke0 ' value for use with the Marsh pharmacokinetic model for propofol.

Anaesthesia (2014-04-18)
A J Thomson, A F Nimmo, F H M Engbers, J B Glen
ABSTRACT

Debate continues over the most appropriate blood-brain equilibration rate constant (ke0) for use with the Marsh pharmacokinetic model for propofol. We aimed to define the optimal ke0 value. Sixty-four patients were sedated with incremental increases in effect-site target concentration of propofol while using six different ke0 values within the range 0.2-1.2 min(-1). Depth of sedation was assessed by measuring visual reaction time. A median 'apparent ke0' value of 0.61 min(-1) (95% CI 0.37-0.78 min(-1)) led to the greatest probability of achieving a stable clinical effect when the effect-site target was fixed at the effect-site concentration displayed by the target-controlled infusion system, at the time when a desired depth of sedation had been reached. By utilising a clinically relevant endpoint to derive this value, inter-individual pharmacokinetic and pharmacodynamic variability may be accounted for.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
2,6-Diisopropylphenol, 97%
Propofol, European Pharmacopoeia (EP) Reference Standard
Supelco
2,6-Diisopropylphenol, analytical standard