Diclofenac pharmacokinetic meta-analysis and dose recommendations for surgical pain in children aged 1-12 years

Background: Diclofenac is an effective, opiate‐sparing analgesic for acute pain in children, which is commonly used in pediatric surgical units. Recently, a Cochrane review concluded the major knowledge gap in diclofenac use is dosing information. A pharmacokinetic meta‐analysis has been undertaken with the aim of recommending a dose for children aged 1–12 years. Methods: Studies containing diclofenac pharmacokinetic data were identified during a Cochrane systematic review, and authors were asked to provide raw data. A pooled population analysis was undertaken in NONMEM to define the pharmacokinetics of intravenous, oral, and rectal diclofenac in children. Simulations were performed to recommend a dose yielding an equivalent area under diclofenac concentration–time curve (AUC) to a 50‐mg dispersible tablet in adults. Results: Data from 111 children aged 1–14 years consisting of 375 samples following intravenous, oral suspension, and suppositories were used. Adult dispersible tablet and suspension data were added to provide a reference AUC and support the absorption modeling, respectively. A three‐compartment model described disposition, a dual‐absorption compartment model was used for suspension and dispersible tablet data, and single‐absorption compartment model for suppositories. The estimate of clearance was 16.5 l·h^?1·70 kg^?1 and bioavailabilities were 0.36, 0.63, and 0.35 for suspension, suppository, and dispersible tablets, respectively. Conclusions: Single doses of 0.3 mg·kg^?1 for intravenous, 0.5 mg·kg^?1 for suppositories, and 1 mg·kg^?1 for oral diclofenac in children aged 1–12 years are recommended as they yield a similar AUC to 50 mg in adults.