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

Research output: Contribution to journalArticle

4 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 languageEnglish (US)
Pages (from-to)80-86
Number of pages7
JournalPaediatric anaesthesia
Volume28
Issue number2
DOIs
StatePublished - 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

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    McLay, J. S., Engelhardt, T., Mohammed, B. S., Cameron, G., Cohen, M. N., Galinkin, J. L., Christians, U., Avram, M. J., Henthorn, T. K., Dsida, R. M., & 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