title: Diclofenac pharmacokinetic meta-analysis and dose recommendations for surgical pain in children aged 1-12 years.
abstract: 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.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden. joseph.standing@nhs.net
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Standing
authors.forename: Dick
authors.initials: D
authors.lastname: Tibboel
authors.forename: Reijo
authors.initials: R
authors.lastname: Korpela
authors.forename: Klaus T
authors.initials: KT
authors.lastname: Olkkola
mesh_terms: D000284:Administration, Oral; D000285:Administration, Rectal; D000465:Algorithms; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D001835:Body Weight; D002626:Chemistry, Pharmaceutical; D002648:Child; D002675:Child, Preschool; D004008:Diclofenac / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007223:Infant; D007275:Injections, Intravenous; D008297:Male; D015233:Models, Statistical; D010149:Postoperative Pain / Q000188:drug therapy*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac