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

Summary

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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