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 Dsida, Brian J. Anderson

*Corresponding author for this work

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 (US)
Pages (from-to)80-86
Number of pages7
JournalPaediatric anaesthesia
Volume28
Issue number2
DOIs
StatePublished - Feb 1 2018

Fingerprint

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

Keywords

  • analgesia
  • child
  • ketorolac
  • nonlinear mixed-effects modelling
  • pharmacokinetics

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Anesthesiology and Pain Medicine

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. Paediatric anaesthesia, 28(2), 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 ; Anderson, Brian J. / The pharmacokinetics of intravenous ketorolac in children aged 2 months to 16 years : A population analysis. In: Paediatric anaesthesia. 2018 ; Vol. 28, No. 2. pp. 80-86.
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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.",
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McLay, JS, Engelhardt, T, Mohammed, BS, Cameron, G, Cohen, MN, Galinkin, JL, Christians, U, Avram, MJ, Henthorn, TK, Dsida, R & Anderson, BJ 2018, 'The pharmacokinetics of intravenous ketorolac in children aged 2 months to 16 years: A population analysis', Paediatric anaesthesia, vol. 28, no. 2, pp. 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; Anderson, Brian J.

In: Paediatric anaesthesia, Vol. 28, No. 2, 01.02.2018, p. 80-86.

Research output: Contribution to journalArticle

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

AU - Anderson, Brian J.

PY - 2018/2/1

Y1 - 2018/2/1

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 - analgesia

KW - child

KW - ketorolac

KW - nonlinear mixed-effects modelling

KW - pharmacokinetics

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DO - 10.1111/pan.13302

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