Propofol clearance in morbidly obese children and adolescents: influence of age and body size

Clin Pharmacokinet. 2012 Aug 1;51(8):543-51. doi: 10.2165/11632940-000000000-00000.


Background and 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 46 kg/m(2) (range 31-63 kg/m(2)) 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.

Conclusion: 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: NCT00948597.

Publication types

  • Controlled Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age Factors
  • Anesthetics, Intravenous / administration & dosage
  • Anesthetics, Intravenous / pharmacokinetics
  • Body Weight
  • Child
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Models, Biological*
  • Nonlinear Dynamics
  • Obesity / complications*
  • Obesity, Morbid / complications*
  • Propofol / administration & dosage
  • Propofol / pharmacokinetics*
  • Tissue Distribution


  • Anesthetics, Intravenous
  • Propofol

Associated data