Bellanti, F;
Del Vecchio, GC;
Putti, MC;
Maggio, A;
Filosa, A;
Cosmi, C;
Mangiarini, L;
... Della Pasqua, O; + view all
(2017)
Population pharmacokinetics and dosing recommendations for the use of deferiprone in children younger than 6 years.
British Journal of Clinical Pharmacology
, 83
(3)
pp. 593-602.
10.1111/bcp.13134.
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Abstract
AIMS: Despite long clinical experience with deferiprone, there is limited information on its pharmacokinetics in children < 6 years of age. Here we assess the impact of developmental growth on the pharmacokinetics of deferiprone in this population using a population approach. Based on pharmacokinetic bridging concepts, we also evaluate whether the recommended doses yield appropriate systemic exposure in this group of patients. METHODS: Data from a study in which 18 paediatric patients were enrolled were available for the purposes of this analysis. Patients were randomised to three deferiprone dose levels (8.3, 16.7 and 33.3 mg/kg). Blood samples were collected according to an optimised sampling scheme in which each patient contributed to a maximum of five samples. A population pharmacokinetic model was developed using NONMEM v.7.2. Model selection criteria were based on graphical and statistical summaries. RESULTS: A one-compartment model with first-order absorption and first-order elimination best described the pharmacokinetics of deferiprone. Drug disposition parameters were affected by body weight, with both clearance and volume increasing allometrically with size. Simulation scenarios show that comparable systemic exposure (AUC) is achieved in children and adults after similar dose levels in mg/kg, with median (5-95(th) quantiles) AUC values respectively of 340.6 (223.2-520.0) and 318.5 (200.4-499.0) µmol/L*h at 75 mg/kg/day and 453.7 (297.3-693.0) and 424.2 (266.9-664.0) at 100 mg/kg/day t.i.d. doses. CONCLUSIONS: Based on the current findings, a dosing regimen of 25 mg/kg t.i.d. is recommended in children below 6 years of age, with the possibility of titration up to 33.3 mg/kg t.i.d.
| Type: | Article |
|---|---|
| Title: | Population pharmacokinetics and dosing recommendations for the use of deferiprone in children younger than 6 years |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/bcp.13134 |
| Publisher version: | http://dx.doi.org/10.1111/bcp.13134 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | deferiprone, dose rationale, paediatrics, pharmacokinetic bridging, thalassaemia |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/1516574 |
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