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Paediatric anaesthesia · Feb 2018
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, and Brian J Anderson.
- The Department of Child Health, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK.
- Paediatr Anaesth. 2018 Feb 1; 28 (2): 80-86.
BackgroundIntravenous 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.AimsThe aim of this study was to review age- and weight-related effects on ketorolac pharmacokinetic parameters in children and current dosing schedules.MethodsPooled 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.ResultsThere 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 .ConclusionClearance, 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.© 2017 John Wiley & Sons Ltd.
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