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

Background: Intravenous ketorolac is commonly administered to children for the control of postoperative pain. An effect site EC ₅₀ 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.
(© 2017 John Wiley & Sons Ltd.)