Paediatric propofol pharmacokinetics: a multicentre study

AE Rigby‐Jones; MJ Priston; AR Wolf; JR Sneyd

doi:10.1111/j.1460-9592.2007.02255_9.x

Paediatric propofol pharmacokinetics: a multicentre study

AE Rigby‐Jones, MJ Priston, AR Wolf, JR Sneyd

Faculty of Health

Research output: Contribution to journal › Article › peer-review

Abstract

Introduction: Schuttler and Imhsens propofol pharmacokinetic (PK) model (1) based on pooled adult and paediatric data lacked information for the smallest patients. We conducted a pooled population analysis of available neonatal and paediatric propofol PK data. The variable clinical circumstances of the individual studies allowed us to explore health status as a PK model covariate.Methods: We combined raw propofol blood/plasma concentration vs time data, dosing information and demographic data from eight paediatric studies conducted by six research groups, with our data (2,3). The pooled data set comprised 197 individuals (2315 observations), aged 0.02–12.25 years (2.75–60.5 kg, median 15 kg). In this preliminary population PK analysis using NONMEM, the basic model structure was established before all model parameters were allometrically scaled to body weight. The influence of health status on paediatric propofol PK was explored.Results: In this 3‐compartment preliminary model, postcardiac surgery patients have significantly reduced metabolic clearance rates (31–45% less when compared with healthy children or noncardiac PICU patients). The volume of the deep peripheral compartment in critically ill and postcardiac surgery children is 319% and 205% larger, respectively, than in healthy children, see Table 1. PK values for a child weighing 15 kg Parameter Typical Value 95% Confidence Interval CL (l·min‐1) Healthy 0.614 0.563–0.665 PICU 0.767 0.628–0.906 PICU cardiac 0.421 0.366–0.476 Q2 (l·min‐1) 0.839 0.703–0.975 Q3 (l·min‐1) 0.252 0.221–0.283 V1 (l) 7.76 6.33–9.19 V2 (l) 14.4 12.8–16.0 V3 (l) Healthy 83.9 61.4–106 PICU 268 183–353 PICU cardiac 172 117–227

Original language	English
Pages (from-to)	610-610
Number of pages	0
Journal	Pediatric Anesthesia
Volume	17
Issue number	6
Early online date	7 May 2007
DOIs	https://doi.org/10.1111/j.1460-9592.2007.02255_9.x
Publication status	Published - Jun 2007

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title = "Paediatric propofol pharmacokinetics: a multicentre study",

abstract = "Introduction: Schuttler and Imhsens propofol pharmacokinetic (PK) model (1) based on pooled adult and paediatric data lacked information for the smallest patients. We conducted a pooled population analysis of available neonatal and paediatric propofol PK data. The variable clinical circumstances of the individual studies allowed us to explore health status as a PK model covariate.Methods: We combined raw propofol blood/plasma concentration vs time data, dosing information and demographic data from eight paediatric studies conducted by six research groups, with our data (2,3). The pooled data set comprised 197 individuals (2315 observations), aged 0.02–12.25 years (2.75–60.5 kg, median 15 kg). In this preliminary population PK analysis using NONMEM, the basic model structure was established before all model parameters were allometrically scaled to body weight. The influence of health status on paediatric propofol PK was explored.Results: In this 3‐compartment preliminary model, postcardiac surgery patients have significantly reduced metabolic clearance rates (31–45% less when compared with healthy children or noncardiac PICU patients). The volume of the deep peripheral compartment in critically ill and postcardiac surgery children is 319% and 205% larger, respectively, than in healthy children, see Table 1. PK values for a child weighing 15 kg Parameter Typical Value 95% Confidence Interval CL (l·min‐1) Healthy 0.614 0.563–0.665 PICU 0.767 0.628–0.906 PICU cardiac 0.421 0.366–0.476 Q2 (l·min‐1) 0.839 0.703–0.975 Q3 (l·min‐1) 0.252 0.221–0.283 V1 (l) 7.76 6.33–9.19 V2 (l) 14.4 12.8–16.0 V3 (l) Healthy 83.9 61.4–106 PICU 268 183–353 PICU cardiac 172 117–227 ",

author = "AE Rigby‐Jones and MJ Priston and AR Wolf and JR Sneyd",

year = "2007",

month = jun,

doi = "10.1111/j.1460-9592.2007.02255_9.x",

language = "English",

volume = "17",

pages = "610--610",

journal = "Pediatric Anesthesia",

issn = "1155-5645",

number = "6",

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TY - JOUR

T1 - Paediatric propofol pharmacokinetics: a multicentre study

AU - Rigby‐Jones, AE

AU - Priston, MJ

AU - Wolf, AR

AU - Sneyd, JR

PY - 2007/6

Y1 - 2007/6

N2 - Introduction: Schuttler and Imhsens propofol pharmacokinetic (PK) model (1) based on pooled adult and paediatric data lacked information for the smallest patients. We conducted a pooled population analysis of available neonatal and paediatric propofol PK data. The variable clinical circumstances of the individual studies allowed us to explore health status as a PK model covariate.Methods: We combined raw propofol blood/plasma concentration vs time data, dosing information and demographic data from eight paediatric studies conducted by six research groups, with our data (2,3). The pooled data set comprised 197 individuals (2315 observations), aged 0.02–12.25 years (2.75–60.5 kg, median 15 kg). In this preliminary population PK analysis using NONMEM, the basic model structure was established before all model parameters were allometrically scaled to body weight. The influence of health status on paediatric propofol PK was explored.Results: In this 3‐compartment preliminary model, postcardiac surgery patients have significantly reduced metabolic clearance rates (31–45% less when compared with healthy children or noncardiac PICU patients). The volume of the deep peripheral compartment in critically ill and postcardiac surgery children is 319% and 205% larger, respectively, than in healthy children, see Table 1. PK values for a child weighing 15 kg Parameter Typical Value 95% Confidence Interval CL (l·min‐1) Healthy 0.614 0.563–0.665 PICU 0.767 0.628–0.906 PICU cardiac 0.421 0.366–0.476 Q2 (l·min‐1) 0.839 0.703–0.975 Q3 (l·min‐1) 0.252 0.221–0.283 V1 (l) 7.76 6.33–9.19 V2 (l) 14.4 12.8–16.0 V3 (l) Healthy 83.9 61.4–106 PICU 268 183–353 PICU cardiac 172 117–227

AB - Introduction: Schuttler and Imhsens propofol pharmacokinetic (PK) model (1) based on pooled adult and paediatric data lacked information for the smallest patients. We conducted a pooled population analysis of available neonatal and paediatric propofol PK data. The variable clinical circumstances of the individual studies allowed us to explore health status as a PK model covariate.Methods: We combined raw propofol blood/plasma concentration vs time data, dosing information and demographic data from eight paediatric studies conducted by six research groups, with our data (2,3). The pooled data set comprised 197 individuals (2315 observations), aged 0.02–12.25 years (2.75–60.5 kg, median 15 kg). In this preliminary population PK analysis using NONMEM, the basic model structure was established before all model parameters were allometrically scaled to body weight. The influence of health status on paediatric propofol PK was explored.Results: In this 3‐compartment preliminary model, postcardiac surgery patients have significantly reduced metabolic clearance rates (31–45% less when compared with healthy children or noncardiac PICU patients). The volume of the deep peripheral compartment in critically ill and postcardiac surgery children is 319% and 205% larger, respectively, than in healthy children, see Table 1. PK values for a child weighing 15 kg Parameter Typical Value 95% Confidence Interval CL (l·min‐1) Healthy 0.614 0.563–0.665 PICU 0.767 0.628–0.906 PICU cardiac 0.421 0.366–0.476 Q2 (l·min‐1) 0.839 0.703–0.975 Q3 (l·min‐1) 0.252 0.221–0.283 V1 (l) 7.76 6.33–9.19 V2 (l) 14.4 12.8–16.0 V3 (l) Healthy 83.9 61.4–106 PICU 268 183–353 PICU cardiac 172 117–227

U2 - 10.1111/j.1460-9592.2007.02255_9.x

DO - 10.1111/j.1460-9592.2007.02255_9.x

M3 - Article

SN - 1155-5645

VL - 17

SP - 610

EP - 610

JO - Pediatric Anesthesia

JF - Pediatric Anesthesia

IS - 6

ER -

Paediatric propofol pharmacokinetics: a multicentre study

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