van Dijkman, SC;
Alvarez-Jimenez, R;
Danhof, M;
Della Pasqua, O;
(2016)
Pharmacotherapy in paediatric epilepsy: from trial and error to rational drug and dose selection – a long way to go.
Expert Opinion in Drug Metabolism and Toxicology
, 12
(10)
pp. 1143-1156.
10.1080/17425255.2016.1203900.
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Abstract
Whereas ongoing efforts in epilepsy research focus on the underlying disease processes, the lack of a physiologically-based rationale for drug and dose selection contributes to inadequate treatment response in children. In fact, limited information on the interindividual variation in pharmacokinetics and pharmacodynamics of anti-epileptic drugs (AEDs) in children drive prescription practice, which relies primarily on dose regimens according to a mg/kg basis. Such practice has evolved despite advancements in paediatric pharmacology showing that growth and maturation processes do not correlate linearly with changes in body size. Areas covered: In this review we aim to provide 1) a comprehensive overview of the sources of variability in the response to AEDs, 2) insight into novel methodologies to characterise such variation and 3) recommendations for treatment personalisation. Expert Opinion: The use of pharmacokinetic-pharmacodynamic principles in clinical practice is hindered by the lack of biomarkers and by practical constraints in the evaluation of polytherapy. The identification of biomarkers and their validation as tools for drug development and therapeutics will require some time. Meanwhile, one should not miss the opportunity to integrate the available pharmacokinetic data with modelling and simulation concepts to prevent further delays in the development of personalised treatments for paediatric patients.
| Type: | Article |
|---|---|
| Title: | Pharmacotherapy in paediatric epilepsy: from trial and error to rational drug and dose selection – a long way to go |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1080/17425255.2016.1203900 |
| Publisher version: | http://dx.doi.org/10.1080/17425255.2016.1203900 |
| Language: | English |
| Additional information: | Copyright © 2016 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. |
| Keywords: | Antiepileptic drugs, dose rationale, epilepsy, epileptic seizures, modelling and simulation, paediatrics, personalised medicine, pharmacokinetics, pharmacokineticpharmacodynamic relationships, translational pharmacology |
| UCL classification: | UCL 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.ucl.ac.uk/id/eprint/1500857 |
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