title: Propofol Clearance in Morbidly Obese Children and Adolescents : Influence of Age and Body Size.
abstract: OBJECTIVE
  Given the alarming increase in obesity among children undergoing surgery, the main aim of this study was to characterize propofol clearance in a cohort of morbidly obese children and adolescents in relation to their age and body weight characteristics.
  
  
  METHODS
  A prospective pharmacokinetic study in morbidly obese children and adolescents undergoing elective surgery was conducted. Serial blood samples were collected and nonlinear mixed-effects modelling using NONMEM® was performed to characterize propofol pharmacokinetics with subsequent evaluation of age and body size descriptors.
  
  
  RESULTS
  Twenty obese and morbidly obese children and adolescents with a mean age of 16 years (range 9-18 years), a mean total body weight (TBW) of 125 kg (range 70-184 kg) and a mean body mass index of 46kg/m2(range 31-63 kg/m2) were available for pharmacokinetic modelling using a two-compartment pharmacokinetic model (n = 294 propofol concentration measurements). Compared with lean body weight and ideal body weight, TBW proved to be the most predictive covariate for clearance [CL (L/min)= 1.70 × (TBW/70)0.8]. Central volume of distribution, peripheral volume and intercompartmental clearance were 45.2 L, 128 L and 1.75 L/min, respectively, with no predictive covariates identifiable.
  
  
  CONCLUSIONS
  In the population pharmacokinetic model for propofol in morbidly obese children and adolescents, TBW proved to be the most significant determinant for clearance. As a result, it is anticipated that dosage of propofol for maintenance of anaesthesia in morbidly obese children and adolescents should be based on TBW using an allometric function. TRIAL REGISTRATION NUMBER (CLINICALTRIALS.GOV): NCT00948597.
authors.affiliation: Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein, the Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Diepstraten
authors.affiliation: Division of Pediatric Anesthesia, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.|Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Vidya
authors.initials: V
authors.lastname: Chidambaran
authors.affiliation: Division of Pediatric Anesthesia, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.|Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Senthilkumar
authors.initials: S
authors.lastname: Sadhasivam
authors.affiliation: Division of Pediatric Anesthesia, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors.forename: Hope R
authors.initials: HR
authors.lastname: Esslinger
authors.affiliation: Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors.forename: Shareen L
authors.initials: SL
authors.lastname: Cox
authors.affiliation: Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.|Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Inge
authors.affiliation: Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein, the Netherlands.|Division of Pharmacology, Leiden/Amsterdam Center for Drug Research, Leiden, the Netherlands.
authors.forename: Catherijne A J
authors.initials: CA
authors.lastname: Knibbe
authors.affiliation: Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA. Sander.Vinks@cchmc.org.|Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. Sander.Vinks@cchmc.org.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Vinks