title: Pharmacodynamic response modelling of arterial blood pressure in adult volunteers during propofol anaesthesia.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Anaesthesiology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Krankenhausstr. 12, Erlangen 91054, Germany christian.jeleazcov@kfa.imed.uni-erlangen.de.
authors: C
authors: C
authors: Jeleazcov
authors: Le Département de Mathématiques de la Faculté des Sciences d'Orsay, Université Paris-Sud, Bat 425, Orsay Cedex 91405, France.
authors: M
authors: M
authors: Lavielle
authors: Department of Anaesthesiology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Krankenhausstr. 12, Erlangen 91054, Germany.
authors: J
authors: J
authors: Schüttler
authors: Department of Anaesthesiology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Krankenhausstr. 12, Erlangen 91054, Germany.
authors: H
authors: H
authors: Ihmsen
mesh_terms: D000293:Adolescent; D000328:Adult; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D062186:Arterial Pressure / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D008954:Models, Biological; D015742:Propofol / Q000493:pharmacokinetics / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D018686:Anesthetics, Intravenous; D015742:Propofol
keywords: arterial pressure; models; pharmacodynamics; propofol