Standing, J.F., Howard, R.F., Johnson, A., Savage, I. and Wong, I.C.K. (2008) Population pharmacokinetics of oral diclofenac for acute pain in children. British Journal of Clinical Pharmacology, 66 (6). pp. 846-853. 10.1111/j.1365-2125.2008.03289.x.
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AIMS 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. METHODS 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. RESULTS 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 VD/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 VD 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. CONCLUSIONS 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.
|Additional Information:||Full text available in print and electronically from the School of Pharmacy Library.|
|Uncontrolled Keywords:||acute pain;children;diclofenac;NONMEM;population pharmacokinetics|
|Departments, units and centres:||Department of Practice and Policy > Department of Practice and Policy|
|Journal or Publication Title:||British Journal of Clinical Pharmacology|
|Deposited By:||Library Staff|
|Deposited On:||21 Dec 2009 14:51|
|Last Modified:||20 Oct 2011 12:10|
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