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


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.
Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein, The Netherlands.
Jeroen
J
Diepstraten
Vidya
V
Chidambaran
Senthilkumar
S
Sadhasivam
Hope R
HR
Esslinger
Shareen L
SL
Cox
Thomas H
TH
Inge
Catherijne A J
CA
Knibbe
Alexander A
AA
Vinks
D000293:Adolescent; D000367:Age Factors; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000493:pharmacokinetics; D001835:Body Weight; D002648:Child; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008954:Models, Biological; D017711:Nonlinear Dynamics; D009765:Obesity / Q000150:complications*; D009767:Obesity, Morbid / Q000150:complications*; D015742:Propofol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D018686:Anesthetics, Intravenous; D015742:Propofol