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.

Additional Metadata
Keywords Cochrane Library, NONMEM, area under the curve, article, child, diclofenac, dispersible tablet, drug bioavailability, drug clearance, human, major clinical study, pharmacokinetics, postoperative pain, priority journal, single drug dose
Persistent URL dx.doi.org/10.1111/j.1460-9592.2010.03509.x, hdl.handle.net/1765/23134
Journal Paediatric Anaesthesia
Citation
Standing, J.F, Tibboel, D, Korpela, R, & Olkkola, K.T. (2011). Diclofenac pharmacokinetic meta-analysis and dose recommendations for surgical pain in children aged 1-12 years. Paediatric Anaesthesia, 21(3), 316–324. doi:10.1111/j.1460-9592.2010.03509.x