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- Standing, Joseph F., et al.
(författare)
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Population pharmacokinetics of oral diclofenac for acute pain in children
- 2008
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Ingår i: British Journal of Clinical Pharmacology. - : Wiley. - 0306-5251 .- 1365-2125. ; 66:6, s. 846-853
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Tidskriftsartikel (refereegranskat)abstract
- WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT center dot Diclofenac is an effective oral analgesic for acute postoperative pain. In adults 25 mg is half as effective as 50 mg, but 50 mg and 100 mg are similarly effective (ceiling effect). Diclofenac has linear pharmacokinetics in this range.center dot Diclofenac is frequently used 'off-label' in children for acute pain but optimum dosing is unclear (dosing of diclofenac in clinical paediatric studies ranges from 0.5-2.5 mg kg(-1)). There is currently no licensed oral paediatric formulation of diclofenac. WHAT THIS STUDY ADDS center dot Using a new diclofenac oral suspension, a dose of 1 mg kg(-1) in children aged 1 to 12 years gives a similar exposure to 50 mg in adults; paediatric patients are unlikely to benefit from higher doses.To develop a population pharmacokinetic model for a new diclofenac suspension (50 mg 5 ml(-1)) in adult volunteers and paediatric patients, and recommend a dose for acute pain in children.Blood samples were drawn at the start and end of surgery, and on removal of the venous cannula from 70 children (aged 1 to 12 years, weight 9 to 37 kg) who received a preoperative oral 1 mg kg(-1) dose; these were pooled with rich (14 post-dose samples) data from 30 adult volunteers. Population pharmacokinetic modelling was undertaken with NONMEM. The optimum adult dose of diclofenac for acute pain is 50 mg. Simulation from the final model was performed to predict a paediatric dose to achieve a similar AUC to 50 mg in adults.A total of 558 serum diclofenac concentrations from 100 subjects was used in the pooled analysis. A single disposition compartment model with first order elimination and dual absorption compartments was used. The estimates of CL/F and V-D/F were 53.98 l h(-1) 70 kg(-1) and 4.84 l 70 kg(-1) respectively. Allometric size models appeared to predict adequately changes in CL and V-D with age. Of the simulated doses investigated, 1 mg kg(-1) gave paediatric AUC((0,12 h)) to adult 50 mg AUC((0,12 h)) ratios of 1.00, 1.08 and 1.18 for ages 1-3, 4-6 and 7-12 years respectively.This study has shown 1 mg kg(-1) diclofenac to produce similar exposure in children aged 1 to 12 years as 50 mg in adults, and is acceptable for clinical practice; patients are unlikely to obtain further benefit from higher doses.
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| 2. |
- Standing, Joseph F, et al.
(författare)
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Prospective observational study of adverse drug reactions to diclofenac in children
- 2009
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Ingår i: British Journal of Clinical Pharmacology. - : Wiley. - 0306-5251 .- 1365-2125. ; 68:2, s. 243-251
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Tidskriftsartikel (refereegranskat)abstract
- center dot Diclofenac is frequently used off-label in children for acute pain, but little information is available on diclofenac adverse drug reactions in this population. WHAT THIS STUDY ADDS center dot The common adverse drug reactions of diclofenac for acute pain in children are of a similar type to those seen in adults. center dot Serious adverse reactions occur in < 0.8% of children and the incidence of diclofenac-induced bronchospasm in asthmatic children is < 2.7%. AIM The aim of this study was to investigate the type of common (occurring in > 1% of patients) adverse reactions caused by diclofenac when given to children for acute pain. METHODS A prospective observational study was undertaken on paediatric surgical patents aged < 12 years at Great Ormond Street and University College London Hospitals. All adverse events were recorded, and causality assessment used to judge the likelihood of them being due to diclofenac. Prospective recruitment meant not all patients were prescribed diclofenac, allowing an analysis of utilization. Causality of all serious adverse events was reviewed by an expert panel. RESULTS Children prescribed diclofenac were significantly older, and stayed in hospital for shorter periods than those who were not. Diclofenac was not avoided in asthmatic patients. Data on 380 children showed they suffer similar types of nonserious adverse reactions to adults. The incidence (95% confidence interval) of rash was 0.8% (0.016, 2.3); minor central nervous system disturbance 0.5% (0.06, 1.9); rectal irritation with suppositories 0.3% (0.009, 1.9); and diarrhoea 0.3% (0.007, 1.5). No serious adverse event was judged to be caused by diclofenac, meaning the incidence of serious adverse reactions to diclofenac in children is < 0.8%. CONCLUSION Children given diclofenac for acute pain appeared to suffer similar types of adverse reactions to adults; the incidence of serious adverse reaction is < 0.8%.
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