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

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

8 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 language	English
Pages (from-to)	80-86
Number of pages	7
Journal	Pediatric Anesthesia
Volume	28
Issue number	2
Early online date	21 Dec 2017
DOIs	https://doi.org/10.1111/pan.13302
Publication status	Published - 28 Feb 2018

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

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@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 = feb,

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

C2 - 29266539

VL - 28

SP - 80

EP - 86

JO - Pediatric Anesthesia

JF - Pediatric Anesthesia

SN - 1155-5645

IS - 2

ER -

The pharmacokinetics of intravenous ketorolac in children aged 2 months to 16 years: A population analysis

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