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

doi:10.1111/pan.13302

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

^*Corresponding author for this work

Anesthesiology

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

6 Scopus citations

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 language	English (US)
Pages (from-to)	80-86
Number of pages	7
Journal	Paediatric anaesthesia
Volume	28
Issue number	2
DOIs	https://doi.org/10.1111/pan.13302
State	Published - Feb 1 2018

Keywords

analgesia
child
ketorolac
nonlinear mixed-effects modelling
pharmacokinetics

ASJC Scopus subject areas

Pediatrics, Perinatology, and Child Health
Anesthesiology and Pain Medicine

Access to Document

10.1111/pan.13302

Fingerprint Dive into the research topics of 'The pharmacokinetics of intravenous ketorolac in children aged 2 months to 16 years: A population analysis'. Together they form a unique fingerprint.

Cite this

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: Paediatric anaesthesia. 2018 ; Vol. 28, No. 2. pp. 80-86.

@article{581d8bdb55854f39b45bb754d094c032,

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 = "analgesia, child, ketorolac, nonlinear 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 = "Funding Information: 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.",

year = "2018",

month = feb,

day = "1",

doi = "10.1111/pan.13302",

language = "English (US)",

volume = "28",

pages = "80--86",

journal = "Paediatric Anaesthesia",

issn = "1155-5645",

publisher = "Wiley-Blackwell",

number = "2",

}

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

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

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 - Funding Information: 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.

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

UR - http://www.scopus.com/inward/record.url?scp=85040793885&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85040793885&partnerID=8YFLogxK

U2 - 10.1111/pan.13302

DO - 10.1111/pan.13302

M3 - Article

C2 - 29266539

AN - SCOPUS:85040793885

VL - 28

SP - 80

EP - 86

JO - Paediatric Anaesthesia

JF - Paediatric Anaesthesia

SN - 1155-5645

IS - 2