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Title: Diclofenac for acute pain in children : pharmacokinetics and safety
Author: Standing, J. F.
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2007
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Abstract:
Diclofenac is commonly used 'off-label' for acute pain in children, and it has been shown to be effective for this indication. There is a five-fold range (0.5 to 2.5mg/kg) in dosing of diclofenac for acute pain in paediatric clinical studies, and little published safety information is available. The metabolism of diclofenac to 4'-hydroxydiclofenac is mediated by CYP2C9, the expression of which may differ during development. Three studies have been undertaken to answer the questions: What dose of diclofenac should be given to children with acute pain What are the adverse effects of diclofenac in children treated for acute pain Does the expression of CYP2C9 change with age in children aged one to 12 years The three studies carried out were: A population pharmacokinetic study on a paediatric day surgery ward investigating a new diclofenac oral suspension, results pooled with adult data supplied by the manufacturer and analysed with NONMEM to produce dosing guidelines a clinical safety study to ascertain common adverse reactions of diclofenac in children with acute pain, followed by a systematic literature review to investigate the type and incidence of rare adverse effects and an investigation of the influence of age and CYP2C9 genotype on the formation of 4'- hydroxydiclofenac in children aged one to 12 years using data collected during the pharmacokinetic study. The optimum dose of diclofenac for acute pain in children is lmg/kg. Diclofenac appeared to cause similar types of adverse reactions in children and adults, although the incidence of gastrointestinal bleeding is possibly lower in children. When diclofenac is used as part of the analgesic regimen in the peri-operative period, children suffer less nausea and vomiting, and no increase in operative bleeding. No differences were found in the expression of CYP2C9 estimated using diclofenac 4'-hydroxylation in children aged one to 12 years, which would appear to confirm in vitro findings in paediatric liver samples.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.719051  DOI: Not available
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