The pharmacokinetics of intravenous ketorolac in children aged 2 months to 16 years

A population analysis

James S McLay, Thomas Engelhardt, Baba S Mohammed, Gary Cameron, Mindy N Cohen, Jeffrey L Galinkin, Uwe Christians, Michael J Avram, Thomas K Henthorn, Richard M Dsida, Brian J Anderson

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

BACKGROUND: Intravenous ketorolac is commonly administered to children for the control of postoperative pain. An effect site EC50 for analgesia of 0.37 mg. L-1 is described in adults.

AIMS: The aim of this study was to review age- and weight-related effects on ketorolac pharmacokinetic parameters in children and current dosing schedules.

METHODS: Pooled intravenous ketorolac (0.5 mg. kg-1 ) concentration-time data in children aged 2 months to 16 years were analyzed using nonlinear mixed-effects models. Allometry was used to scale to a 70 kg person.

RESULTS: There were 64 children aged 2 months to 16 years (641 plasma concentrations) available for analysis. A two-compartment mammillary model was used to describe pharmacokinetics. Clearance was 2.53 (CV 45.9%) L. h-1. 70 kg-1 and intercompartment clearance was 4.43 (CV 95.6%) L. h-1. 70 kg-1 . Both central (V1) and peripheral (V2) volumes of distribution decreased with age over the first few years of postnatal life to reach V1 6.89 (CV 30.3%) L. 70 kg-1 and V2 5.53 (CV 47.6%) L. 70 kg-1 .

CONCLUSION: Clearance, expressed as L. h-1. kg-1 , decreased with age from infancy. A dosing regimen of 0.5 mg. kg-1 every 6 hours maintains a trough concentration larger than 0.37 mg. L-1 in children 9 months to 16 years of age. This dosing regimen is consistent with current recommendations.

Original languageEnglish
Pages (from-to)80-86
Number of pages7
JournalPediatric Anesthesia
Volume28
Issue number2
Early online date21 Dec 2017
DOIs
Publication statusPublished - 28 Feb 2018

Fingerprint

Ketorolac
Pharmacokinetics
Population
Postoperative Pain
Analgesia
Appointments and Schedules
Weights and Measures

Keywords

  • Journal Article
  • analgesia
  • child
  • ketorolac
  • nonlinear mixed-effects modellingnonlinear mixed-effects modellingnonlinear mixed-effects modellingnonlinear mixed-effects modellingnonlinear mixed-effects modellingnonlinear mixed-effects modelling
  • pharmacokinetics

Cite this

McLay, J. S., Engelhardt, T., Mohammed, B. S., Cameron, G., Cohen, M. N., Galinkin, J. L., ... Anderson, B. J. (2018). The pharmacokinetics of intravenous ketorolac in children aged 2 months to 16 years: A population analysis. Pediatric Anesthesia, 28(2), 80-86. https://doi.org/10.1111/pan.13302

The pharmacokinetics of intravenous ketorolac in children aged 2 months to 16 years : A population analysis. / McLay, James S; Engelhardt, Thomas; Mohammed, Baba S; Cameron, Gary; Cohen, Mindy N; Galinkin, Jeffrey L; Christians, Uwe; Avram, Michael J; Henthorn, Thomas K; Dsida, Richard M; Anderson, Brian J.

In: Pediatric Anesthesia, Vol. 28, No. 2, 28.02.2018, p. 80-86.

Research output: Contribution to journalArticle

McLay, JS, Engelhardt, T, Mohammed, BS, Cameron, G, Cohen, MN, Galinkin, JL, Christians, U, Avram, MJ, Henthorn, TK, Dsida, RM & Anderson, BJ 2018, 'The pharmacokinetics of intravenous ketorolac in children aged 2 months to 16 years: A population analysis', Pediatric Anesthesia, vol. 28, no. 2, pp. 80-86. https://doi.org/10.1111/pan.13302
McLay, James S ; Engelhardt, Thomas ; Mohammed, Baba S ; Cameron, Gary ; Cohen, Mindy N ; Galinkin, Jeffrey L ; Christians, Uwe ; Avram, Michael J ; Henthorn, Thomas K ; Dsida, Richard M ; Anderson, Brian J. / The pharmacokinetics of intravenous ketorolac in children aged 2 months to 16 years : A population analysis. In: Pediatric Anesthesia. 2018 ; Vol. 28, No. 2. pp. 80-86.
@article{7d8f9a7d51df4aeab7fe9646e82e1cae,
title = "The pharmacokinetics of intravenous ketorolac in children aged 2 months to 16 years: A population analysis",
abstract = "BACKGROUND: Intravenous ketorolac is commonly administered to children for the control of postoperative pain. An effect site EC50 for analgesia of 0.37 mg. L-1 is described in adults.AIMS: The aim of this study was to review age- and weight-related effects on ketorolac pharmacokinetic parameters in children and current dosing schedules.METHODS: Pooled intravenous ketorolac (0.5 mg. kg-1 ) concentration-time data in children aged 2 months to 16 years were analyzed using nonlinear mixed-effects models. Allometry was used to scale to a 70 kg person.RESULTS: There were 64 children aged 2 months to 16 years (641 plasma concentrations) available for analysis. A two-compartment mammillary model was used to describe pharmacokinetics. Clearance was 2.53 (CV 45.9{\%}) L. h-1. 70 kg-1 and intercompartment clearance was 4.43 (CV 95.6{\%}) L. h-1. 70 kg-1 . Both central (V1) and peripheral (V2) volumes of distribution decreased with age over the first few years of postnatal life to reach V1 6.89 (CV 30.3{\%}) L. 70 kg-1 and V2 5.53 (CV 47.6{\%}) L. 70 kg-1 .CONCLUSION: Clearance, expressed as L. h-1. kg-1 , decreased with age from infancy. A dosing regimen of 0.5 mg. kg-1 every 6 hours maintains a trough concentration larger than 0.37 mg. L-1 in children 9 months to 16 years of age. This dosing regimen is consistent with current recommendations.",
keywords = "Journal Article, analgesia, child, ketorolac, nonlinear mixed-effects modellingnonlinear mixed-effects modellingnonlinear mixed-effects modellingnonlinear mixed-effects modellingnonlinear mixed-effects modellingnonlinear mixed-effects modelling, pharmacokinetics",
author = "McLay, {James S} and Thomas Engelhardt and Mohammed, {Baba S} and Gary Cameron and Cohen, {Mindy N} and Galinkin, {Jeffrey L} and Uwe Christians and Avram, {Michael J} and Henthorn, {Thomas K} and Dsida, {Richard M} and Anderson, {Brian J}",
note = "ACKNOWLEDGMENTS This work was carried out under the auspices of the Scottish Children Research Network (ScotCRN), a center for mounting clinical trials and addressing the knowledge gaps in support of the effective and safe use of medicines in children. Funding information: This work was funded from institutional resources.",
year = "2018",
month = "2",
day = "28",
doi = "10.1111/pan.13302",
language = "English",
volume = "28",
pages = "80--86",
journal = "Pediatric Anesthesia",
issn = "1155-5645",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - The pharmacokinetics of intravenous ketorolac in children aged 2 months to 16 years

T2 - A population analysis

AU - McLay, James S

AU - Engelhardt, Thomas

AU - Mohammed, Baba S

AU - Cameron, Gary

AU - Cohen, Mindy N

AU - Galinkin, Jeffrey L

AU - Christians, Uwe

AU - Avram, Michael J

AU - Henthorn, Thomas K

AU - Dsida, Richard M

AU - Anderson, Brian J

N1 - ACKNOWLEDGMENTS This work was carried out under the auspices of the Scottish Children Research Network (ScotCRN), a center for mounting clinical trials and addressing the knowledge gaps in support of the effective and safe use of medicines in children. Funding information: This work was funded from institutional resources.

PY - 2018/2/28

Y1 - 2018/2/28

N2 - BACKGROUND: Intravenous ketorolac is commonly administered to children for the control of postoperative pain. An effect site EC50 for analgesia of 0.37 mg. L-1 is described in adults.AIMS: The aim of this study was to review age- and weight-related effects on ketorolac pharmacokinetic parameters in children and current dosing schedules.METHODS: Pooled intravenous ketorolac (0.5 mg. kg-1 ) concentration-time data in children aged 2 months to 16 years were analyzed using nonlinear mixed-effects models. Allometry was used to scale to a 70 kg person.RESULTS: There were 64 children aged 2 months to 16 years (641 plasma concentrations) available for analysis. A two-compartment mammillary model was used to describe pharmacokinetics. Clearance was 2.53 (CV 45.9%) L. h-1. 70 kg-1 and intercompartment clearance was 4.43 (CV 95.6%) L. h-1. 70 kg-1 . Both central (V1) and peripheral (V2) volumes of distribution decreased with age over the first few years of postnatal life to reach V1 6.89 (CV 30.3%) L. 70 kg-1 and V2 5.53 (CV 47.6%) L. 70 kg-1 .CONCLUSION: Clearance, expressed as L. h-1. kg-1 , decreased with age from infancy. A dosing regimen of 0.5 mg. kg-1 every 6 hours maintains a trough concentration larger than 0.37 mg. L-1 in children 9 months to 16 years of age. This dosing regimen is consistent with current recommendations.

AB - BACKGROUND: Intravenous ketorolac is commonly administered to children for the control of postoperative pain. An effect site EC50 for analgesia of 0.37 mg. L-1 is described in adults.AIMS: The aim of this study was to review age- and weight-related effects on ketorolac pharmacokinetic parameters in children and current dosing schedules.METHODS: Pooled intravenous ketorolac (0.5 mg. kg-1 ) concentration-time data in children aged 2 months to 16 years were analyzed using nonlinear mixed-effects models. Allometry was used to scale to a 70 kg person.RESULTS: There were 64 children aged 2 months to 16 years (641 plasma concentrations) available for analysis. A two-compartment mammillary model was used to describe pharmacokinetics. Clearance was 2.53 (CV 45.9%) L. h-1. 70 kg-1 and intercompartment clearance was 4.43 (CV 95.6%) L. h-1. 70 kg-1 . Both central (V1) and peripheral (V2) volumes of distribution decreased with age over the first few years of postnatal life to reach V1 6.89 (CV 30.3%) L. 70 kg-1 and V2 5.53 (CV 47.6%) L. 70 kg-1 .CONCLUSION: Clearance, expressed as L. h-1. kg-1 , decreased with age from infancy. A dosing regimen of 0.5 mg. kg-1 every 6 hours maintains a trough concentration larger than 0.37 mg. L-1 in children 9 months to 16 years of age. This dosing regimen is consistent with current recommendations.

KW - Journal Article

KW - analgesia

KW - child

KW - ketorolac

KW - nonlinear mixed-effects modellingnonlinear mixed-effects modellingnonlinear mixed-effects modellingnonlinear mixed-effects modellingnonlinear mixed-effects modellingnonlinear mixed-effects modelling

KW - pharmacokinetics

U2 - 10.1111/pan.13302

DO - 10.1111/pan.13302

M3 - Article

VL - 28

SP - 80

EP - 86

JO - Pediatric Anesthesia

JF - Pediatric Anesthesia

SN - 1155-5645

IS - 2

ER -