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Individualised dosing algorithms and therapeutic monitoring for antiepileptic drugs

van Dijkman, SC; Wicha, SG; Danhof, M; Della Pasqua, OE; (2018) Individualised dosing algorithms and therapeutic monitoring for antiepileptic drugs. Clinical Pharmacology & Therapeutics , 103 (4) pp. 663-673. 10.1002/cpt.777. Green open access

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Abstract

Pharmacokinetic (PK) models exist for most antiepileptic drugs (AEDs). Yet, their use in clinical practice to assess inter-individual differences and derive individualised doses has been limited. Here we show how model-based dosing algorithms can be used to ensure attainment of target exposure and improve treatment response in patients. Using simulations, different treatment scenarios were explored for 11 commonly used AEDs. For each drug, five scenarios were considered: i. all patients receive the same dose. ii. individual clearance (CL), as predicted by population PK models is used to personalize treatment. iii-v. individual CL, obtained by therapeutic drug monitoring (TDM) according to different sampling schemes is used to personalise treatment. Attainment of steady-state target exposure was used as performance criterion to rank each scenario. In contrast to current clinical guidelines, our results show that patient demographic and clinical characteristics should be used in conjunction with TDM to personalize the treatment of seizures.

Type: Article
Title: Individualised dosing algorithms and therapeutic monitoring for antiepileptic drugs
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/cpt.777
Publisher version: http://dx.doi.org/10.1002/cpt.777
Language: English
Additional information: Copyright © 2017 The Authors. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Keywords: anti-epileptic drugs; pharmacokinetics; pharmacodynamics; drug-drug interactions; personalised medicine; dose rationale
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.ucl.ac.uk/id/eprint/1561459
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