Jeroen Diepstraten1, Vidya Chidambaran2,3, Senthilkumar Sadhasivam2,3, Hope R Esslinger2, Shareen L Cox4, Thomas H Inge3,5, Catherijne A J Knibbe1,6, Alexander A Vinks7,8. 1. Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein, the Netherlands. 2. Division of Pediatric Anesthesia, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. 3. Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA. 4. Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. 5. Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. 6. Division of Pharmacology, Leiden/Amsterdam Center for Drug Research, Leiden, the Netherlands. 7. Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA. Sander.Vinks@cchmc.org. 8. Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. Sander.Vinks@cchmc.org.
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.
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 obesechildren and adolescents in relation to their age and body weight characteristics. METHODS: A prospective pharmacokinetic study in morbidly obesechildren 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 obesechildren 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 obesechildren 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 obesechildren and adolescents should be based on TBW using an allometric function. TRIAL REGISTRATION NUMBER (CLINICALTRIALS.GOV): NCT00948597.
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