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.
- Journal Article
- nonlinear mixed-effects modellingnonlinear mixed-effects modellingnonlinear mixed-effects modellingnonlinear mixed-effects modellingnonlinear mixed-effects modellingnonlinear mixed-effects modelling