Diclofenac pharmacokinetic meta-analysis and dose recommendations for surgical pain in children aged 1-12 years
2011 (English)In: Pediatric Anaesthesia, ISSN 1155-5645, E-ISSN 1460-9592, Vol. 21, no 3, 316-324 p.Article in journal (Refereed) Published
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 16.51.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.
Place, publisher, year, edition, pages
2011. Vol. 21, no 3, 316-324 p.
diclofenac, child, postoperative pain, NONMEM, pharmacokinetics
IdentifiersURN: urn:nbn:se:uu:diva-157671DOI: 10.1111/j.1460-9592.2010.03509.xISI: 000288119900017OAI: oai:DiVA.org:uu-157671DiVA: diva2:436083