Clinical Pharmacokinetics

, Volume 51, Issue 8, pp 543–551

Propofol Clearance in Morbidly Obese Children and Adolescents

Influence of Age and Body Size
  • Jeroen Diepstraten
  • Vidya Chidambaran
  • Senthilkumar Sadhasivam
  • Hope R. Esslinger
  • Shareen L. Cox
  • Thomas H. Inge
  • Catherijne A. J. Knibbe
  • Alexander A. Vinks
Original Research Article

Abstract

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 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.

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 number (clinicaltrials.gov)

NCT00948597

Copyright information

© Springer International Publishing AG 2012

Authors and Affiliations

  • Jeroen Diepstraten
    • 1
  • Vidya Chidambaran
    • 2
    • 3
  • Senthilkumar Sadhasivam
    • 2
    • 3
  • Hope R. Esslinger
    • 2
  • Shareen L. Cox
    • 4
  • Thomas H. Inge
    • 3
    • 5
  • Catherijne A. J. Knibbe
    • 1
    • 6
  • Alexander A. Vinks
    • 3
    • 4
  1. 1.Department of Clinical PharmacySt. Antonius HospitalNieuwegeinthe Netherlands
  2. 2.Division of Pediatric AnesthesiaCincinnati Children’s Hospital Medical CenterCincinnatiUSA
  3. 3.Department of Pediatrics, College of MedicineUniversity of CincinnatiCincinnatiUSA
  4. 4.Division of Clinical PharmacologyCincinnati Children’s Hospital Medical CenterCincinnatiUSA
  5. 5.Division of Pediatric General and Thoracic SurgeryCincinnati Children’s Hospital Medical CenterCincinnatiUSA
  6. 6.Division of PharmacologyLeiden/Amsterdam Center for Drug ResearchLeidenthe Netherlands
  7. 7.Cincinnati Children’s Hospital Medical CenterCincinnatiUSA

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