title: Obesity Does Not Affect Propofol Pharmacokinetics During Hypothermic Cardiopulmonary Bypass.
abstract: OBJECTIVE
  Because of the lack of data regarding the impact of obesity on propofol pharmacokinetics in patients undergoing cardiac surgery using hypothermic cardiopulmonary bypass (CPB), the authors sought to explore propofol pharmacokinetics and develop a predictive pharmacokinetic model that characterizes and predicts propofol pharmacokinetics in this population.
  
  
  METHODS
  A prospective, observational study.
  
  
  METHODS
  A teaching hospital.
  
  
  METHODS
  The study comprised 17 obese and 17 control (nonobese) patients undergoing hypothermic CPB.
  
  
  METHODS
  None.
  
  
  RESULTS
  Patients mainly underwent valve surgery. On initiation of hypothermic CPB (28°C-32°C), patients received a propofol (1%) bolus (1 mg/kg) immediately followed by a 2 mg/kg/h infusion. Blood samples were withdrawn at the following times: before dosing; 1, 3, 5, and 7 minutes after the propofol bolus dose; every 20 minutes during infusion; just before discontinuation of the infusion; and at 1, 3, 5, 7, 10, 20, 30, and 60 minutes after discontinuation of the infusion. The plasma propofol concentration was determined using high-performance liquid chromatography, and then data were imported into Monolix (Lixoft, Antony, France) for population pharmacokinetic modeling and pharmacokinetic parameters estimation. A 2-compartment pharmacokinetic model with age as a covariate on the peripheral volume of distribution (V2) best described the pooled data. The pooled data was internally evaluated successfully to describe and predict propofol pharmacokinetics in the addressed population. Propofol clearance, intercompartmental clearance, and central volume of distribution were 805 mL/min, 1140 mL/min and 18.8 L, respectively. V2 was calculated as 9.86×exp.(1.88×[age/40]) L.
  
  
  CONCLUSIONS
  Propofol pharmacokinetic parameters were similar in obese and nonobese patients undergoing hypothermic CPB. Age was the major determinant of propofol V2 in the obese population.
authors.affiliation: Clinical Pharmacy Department, Faculty of Pharmacy. Electronic address: eman.ali@pharma.cu.edu.eg.
authors.forename: Iman A
authors.initials: IA
authors.lastname: El-Baraky
authors.affiliation: Clinical Pharmacy Department, Faculty of Pharmacy.
authors.forename: Maggie M
authors.initials: MM
authors.lastname: Abbassi
authors.affiliation: Anaesthiology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Tarek A
authors.initials: TA
authors.lastname: Marei
authors.affiliation: Clinical Pharmacy Department, Faculty of Pharmacy.
authors.forename: Nirmeen A
authors.initials: NA
authors.lastname: Sabry
mesh_terms: D000328:Adult; D000367:Age Factors; D018686:Anesthetics, Intravenous / Q000097:blood*; D000886:Anthropometry / Q000379:methods; D001800:Blood Specimen Collection / Q000379:methods; D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass / Q000379:methods*; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005260:Female; D006801:Humans; D007036:Hypothermia, Induced; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009765:Obesity / Q000097:blood*; D015742:Propofol / Q000097:blood*; D011446:Prospective Studies
chemical_list: D018686:Anesthetics, Intravenous; D015742:Propofol
keywords: cardiopulmonary bypass; obesity; pharmacokinetics; propofol