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Pharmacokinetics of S-ketamine during prolonged sedation at the pediatric intensive care unit. / Flint, Robert B.; Brouwer, Carole N. M.; Kränzlin, Anne S. C. et al.

In: Paediatric anaesthesia, Vol. 27, No. 11, 2017, p. 1098-1107.

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Flint, Robert B. ; Brouwer, Carole N. M. ; Kränzlin, Anne S. C. et al. / Pharmacokinetics of S-ketamine during prolonged sedation at the pediatric intensive care unit. In: Paediatric anaesthesia. 2017 ; Vol. 27, No. 11. pp. 1098-1107.

BibTeX

@article{fa7ac18ba7d943198f2874b285f6f3bb,
title = "Pharmacokinetics of S-ketamine during prolonged sedation at the pediatric intensive care unit",
abstract = "BackgroundS-ketamine is the S(+)-enantiomer of the racemic mixture ketamine, an anesthetic drug providing both sedation and analgesia. In clinical practice, significant interpatient variability in drug effect of S-ketamine is observed during long-term sedation. AimsThe aim of this study was to evaluate the pharmacokinetic variability of S-ketamine in children aged 0-18years during long-term sedation. Twenty-five children (median age: 0.42years, range: 0.02-12.5) received continuous intravenous administrations of 0.3-3.6mg/kg/h S-ketamine for sedation during mechanical ventilation. Infusion rates were adjusted to the desired level of sedation and analgesia based on the COMFORT-B score and Visual Analog Scale. Blood samples were drawn once daily at random time-points, and at 1 and 4hours after discontinuation of S-ketamine infusion. Time profiles of plasma concentrations of S-ketamine and active metabolite S-norketamine were analyzed using nonlinear mixed-effects modeling software. Clearance and volume of distribution were allometrically scaled using the power model. ResultsA total of 86 blood samples were collected. A 2-compartment and 1-compartment model adequately described the PK of S-ketamine and S-norketamine, respectively. The typical parameter estimates for clearance and central and peripheral volumes of distribution were: CLS-KETAMINE=112L/h/70kg, V1(S-KETAMINE)=7.7L/70kg, V2(S-KETAMINE)=545L/70kg, Q(S-kETAMINE)=196L/h/70kg, and CLS-NORKETAMINE=53L/h/70kg. Interpatient variability of CLS-KETAMINE and CLS-NORKETAMINE was considerable with values of 40% and 104%, respectively, leading to marked variability in steady-state plasma concentrations. ConclusionSubstantial interpatient variability in pharmacokinetics in children complicates the development of adequate dosage regimen for continuous sedation",
author = "Flint, {Robert B.} and Brouwer, {Carole N. M.} and Kr{\"a}nzlin, {Anne S. C.} and Loraine Lie-A-Huen and Bos, {Albert P.} and Math{\^o}t, {Ron A. A.}",
year = "2017",
doi = "10.1111/pan.13239",
language = "English",
volume = "27",
pages = "1098--1107",
journal = "Paediatric anaesthesia",
issn = "1155-5645",
publisher = "Wiley-Blackwell",
number = "11",

}

RIS

TY - JOUR

T1 - Pharmacokinetics of S-ketamine during prolonged sedation at the pediatric intensive care unit

AU - Flint, Robert B.

AU - Brouwer, Carole N. M.

AU - Kränzlin, Anne S. C.

AU - Lie-A-Huen, Loraine

AU - Bos, Albert P.

AU - Mathôt, Ron A. A.

PY - 2017

Y1 - 2017

N2 - BackgroundS-ketamine is the S(+)-enantiomer of the racemic mixture ketamine, an anesthetic drug providing both sedation and analgesia. In clinical practice, significant interpatient variability in drug effect of S-ketamine is observed during long-term sedation. AimsThe aim of this study was to evaluate the pharmacokinetic variability of S-ketamine in children aged 0-18years during long-term sedation. Twenty-five children (median age: 0.42years, range: 0.02-12.5) received continuous intravenous administrations of 0.3-3.6mg/kg/h S-ketamine for sedation during mechanical ventilation. Infusion rates were adjusted to the desired level of sedation and analgesia based on the COMFORT-B score and Visual Analog Scale. Blood samples were drawn once daily at random time-points, and at 1 and 4hours after discontinuation of S-ketamine infusion. Time profiles of plasma concentrations of S-ketamine and active metabolite S-norketamine were analyzed using nonlinear mixed-effects modeling software. Clearance and volume of distribution were allometrically scaled using the power model. ResultsA total of 86 blood samples were collected. A 2-compartment and 1-compartment model adequately described the PK of S-ketamine and S-norketamine, respectively. The typical parameter estimates for clearance and central and peripheral volumes of distribution were: CLS-KETAMINE=112L/h/70kg, V1(S-KETAMINE)=7.7L/70kg, V2(S-KETAMINE)=545L/70kg, Q(S-kETAMINE)=196L/h/70kg, and CLS-NORKETAMINE=53L/h/70kg. Interpatient variability of CLS-KETAMINE and CLS-NORKETAMINE was considerable with values of 40% and 104%, respectively, leading to marked variability in steady-state plasma concentrations. ConclusionSubstantial interpatient variability in pharmacokinetics in children complicates the development of adequate dosage regimen for continuous sedation

AB - BackgroundS-ketamine is the S(+)-enantiomer of the racemic mixture ketamine, an anesthetic drug providing both sedation and analgesia. In clinical practice, significant interpatient variability in drug effect of S-ketamine is observed during long-term sedation. AimsThe aim of this study was to evaluate the pharmacokinetic variability of S-ketamine in children aged 0-18years during long-term sedation. Twenty-five children (median age: 0.42years, range: 0.02-12.5) received continuous intravenous administrations of 0.3-3.6mg/kg/h S-ketamine for sedation during mechanical ventilation. Infusion rates were adjusted to the desired level of sedation and analgesia based on the COMFORT-B score and Visual Analog Scale. Blood samples were drawn once daily at random time-points, and at 1 and 4hours after discontinuation of S-ketamine infusion. Time profiles of plasma concentrations of S-ketamine and active metabolite S-norketamine were analyzed using nonlinear mixed-effects modeling software. Clearance and volume of distribution were allometrically scaled using the power model. ResultsA total of 86 blood samples were collected. A 2-compartment and 1-compartment model adequately described the PK of S-ketamine and S-norketamine, respectively. The typical parameter estimates for clearance and central and peripheral volumes of distribution were: CLS-KETAMINE=112L/h/70kg, V1(S-KETAMINE)=7.7L/70kg, V2(S-KETAMINE)=545L/70kg, Q(S-kETAMINE)=196L/h/70kg, and CLS-NORKETAMINE=53L/h/70kg. Interpatient variability of CLS-KETAMINE and CLS-NORKETAMINE was considerable with values of 40% and 104%, respectively, leading to marked variability in steady-state plasma concentrations. ConclusionSubstantial interpatient variability in pharmacokinetics in children complicates the development of adequate dosage regimen for continuous sedation

U2 - 10.1111/pan.13239

DO - 10.1111/pan.13239

M3 - Article

C2 - 29030928

VL - 27

SP - 1098

EP - 1107

JO - Paediatric anaesthesia

JF - Paediatric anaesthesia

SN - 1155-5645

IS - 11

ER -

ID: 4118940