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

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.

Paediatr Anaesth. 2017 Dec 22; 28(2):80-86


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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