Pharmacodynamic response modelling of arterial blood pressure in adult volunteers during propofol anaesthesia.

Abstract

Concentration effect relationships are commonly described with a direct response model as for example the sigmoid E(max) model with one effect compartment as site of action. In this study we investigated whether models with more than one effect site, or indirect response, or counter-regulatory response models may be more appropriate for modelling the propofol effect on arterial blood pressure. Nine young healthy volunteers received propofol as target controlled infusion with predefined increasing and decreasing plasma target concentrations. Propofol concentrations were determined from arterial blood samples. Arterial blood pressure was measured invasively at radial artery site. Pharmacokinetic/-pharmacodynamic modelling was performed by population analysis with MONOLIX, testing different direct, indirect and counter-regulatory response models. Propofol plasma concentrations were well described by a three-compartment model. The propofol effect on arterial blood pressure was best described by a direct sigmoid E(max) model with two effect site compartments. Two effect sites were needed to describe the propofol effect on arterial blood pressure. This may reflect different pathways of arterial blood pressure response to propofol.