title: Pharmacokinetics and pharmacodynamics of propofol in children undergoing different types of surgeries.
abstract: BACKGROUND
  Propofol is a commonly used agent in total intravenous anesthesia (TIVA). However, the link between its pharmacokinetics and pharmacodynamics has not been fully characterized in children yet. Our aim was to determine the quantitative relationship between the venous plasma concentration and bispectral index (BIS) effect in a heterogeneous group of pediatric patients undergoing various surgical procedures (ASA status I-III).
  
  
  METHODS
  Nine male and nine female patients were anesthetized with propofol-fentanyl TIVA. Sparse venous samples for propofol concentrations assay and dense BIS measurements were collected during and after the end of infusion. Nonlinear mixed-effect modeling in NONMEM was used for data analysis.
  
  
  RESULTS
  A three-compartment model was linked with a classical Emax model through a biophase compartment to describe the available data. All clearance and volume terms were allometrically scaled to account for the body mass difference among the patients under study. A typical patient had their PK parameters observed within the range of literature values for children. The pharmacodynamic parameters were highly variable. The EC50 of 2.80 mg/L and the biophase distribution rate constant of 3.33 min(-1) were found for a typical patient.
  
  
  CONCLUSIONS
  The BIS values in children are highly correlated with the propofol effect compartment concentrations according to the classical Emax concentration-response relationship. Children had slightly lower sensitivity to propofol and slightly higher clearance, as compared with the adult data available in literature. The intra-patient variations in the BIS require the anesthesiologist's attention in using BIS values alone to evaluate the depth of anesthesia in children.
authors.affiliation: Department of Pediatric Anesthesiology and Intensive Therapy, Poznań University of Medical Sciences, Poznań, Poland.
authors.forename: Alicja
authors.initials: A
authors.lastname: Bartkowska-Śniatkowska
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Poznań University of Medical Sciences, Poznań, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Bienert
authors.affiliation: Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Gdańsk, Poland. Electronic address: wiczling@gumed.edu.pl.
authors.forename: Paweł
authors.initials: P
authors.lastname: Wiczling
authors.affiliation: Department of Anaesthesiology and Intensive Therapy, Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Owczarek
authors.affiliation: Department of Pediatric Anesthesiology and Intensive Therapy, Poznań University of Medical Sciences, Poznań, Poland.
authors.forename: Jowita
authors.initials: J
authors.lastname: Rosada-Kurasińska
authors.affiliation: Department of Teaching Anesthesiology and Intensive Therapy, Poznań University of Medical Sciences, Poznań, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Grześkowiak
authors.affiliation: Department of Analytical Chemistry, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Matysiak
authors.affiliation: Department of Analytical Chemistry, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: Zenon J
authors.initials: ZJ
authors.lastname: Kokot
authors.affiliation: Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: Roman
authors.initials: R
authors.lastname: Kaliszan
authors.affiliation: Department of Clinical Pharmacy and Biopharmacy, Poznań University of Medical Sciences, Poznań, Poland.
authors.forename: Edmund
authors.initials: E
authors.lastname: Grześkowiak
mesh_terms: D000293:Adolescent; D018686:Anesthetics, Intravenous / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D056805:Consciousness Monitors; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage*; D006801:Humans; D007223:Infant; D008297:Male; D008954:Models, Biological; D017711:Nonlinear Dynamics; D015742:Propofol / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D018686:Anesthetics, Intravenous; D005283:Fentanyl; D015742:Propofol
keywords: Bispectral index; Children; Pharmacokinetic and pharmacodynamics modeling; Propofol; Total intravenous anesthesia