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.
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.
Authors: Victoria C Ziesenitz; Tatjana Welzel; Madelé van Dyk; Patrick Saur; Matthias Gorenflo; Johannes N van den Anker Journal: Paediatr Drugs Date: 2022-09-02 Impact factor: 3.930