Optimization of levetiracetam dosing regimen in critically ill patients with augmented renal clearance: a Monte Carlo simulation study
dc.contributor.author | Bilbao Meseguer, Idoia | |
dc.contributor.author | Barrasa González, Helena | |
dc.contributor.author | Rodríguez Gascón, Alicia | |
dc.contributor.author | Asín-Prieto, Eduardo | |
dc.contributor.author | Maynar, Javier | |
dc.contributor.author | Sánchez Izquierdo, José Ángel | |
dc.contributor.author | Solinís Aspiazu, María Ángeles | |
dc.contributor.author | Isla Ruiz, Arantxazu | |
dc.date.accessioned | 2022-04-29T07:37:06Z | |
dc.date.available | 2022-04-29T07:37:06Z | |
dc.date.issued | 2022-04 | |
dc.identifier.citation | Journal of Intensive Care 10 : (2022) // Article ID 21 | es_ES |
dc.identifier.issn | 2052-0492 | |
dc.identifier.uri | http://hdl.handle.net/10810/56421 | |
dc.description.abstract | [EN] Background Levetiracetam pharmacokinetics is extensively altered in critically ill patients with augmented renal clearance (ARC). Consequently, the dosage regimens commonly used in clinical practice may not be sufficient to achieve target plasma concentrations. The aim of this study is to propose alternative dosage regimens able to achieve target concentrations in this population. Furthermore, the feasibility of the proposed dosing regimens will be discussed from a clinical point of view. Methods Different dosage regimens for levetiracetam were evaluated in critically ill patients with ARC. Monte Carlo simulations were conducted with extended or continuous infusions and/or high drug doses using a previously developed population pharmacokinetic model. To assess the clinical feasibility of the proposed dosages, we carried out a literature search to evaluate the information on toxicity and efficacy of continuous administration or high doses, as well as the post-dilution stability of levetiracetam. Results According to the simulations, target concentrations in patients with CrCl of 160 or 200 mL/min can be achieved with the 3000 mg daily dose by prolonging the infusion time of levetiracetam. For patients with CrCl of 240 mL/min, it would be necessary to administer doses higher than the maximum recommended. Available evidence suggests that levetiracetam administration in continuous infusion or at higher doses than those approved seems to be safe. It would be desirable to re-examinate the current recommendations about drug stability and to achieve a consensus in this issue. Conclusions Conventional dosage regimens of levetiracetam (500-1500 mg twice daily in a short infusion) do not allow obtaining drug plasma concentrations among the defined target in critically ill patients with ARC. Therefore, new dosing guidelines with specific recommendations for patients in this subpopulation are needed. This study proposes new dosages for levetiracetam, including extended (4 or 6 h) infusions, continuous infusions or the administration of doses higher than the recommended in the summary of product characteristics (> 3000 mg). These new dosage recommendations take into account biopharmaceutical and pharmacokinetic aspects and meet feasibility criteria, which allow them to be transferred to the clinical environment with safety and efficacy. Nevertheless, further clinical studies are needed to confirm these results. | es_ES |
dc.description.sponsorship | This research was funded by Department of Education of the Basque Government (PIBA 2019-57) and by the University of the Basque Country UPV/EHU (GIU20/048). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | BMC | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | levetiracetam | es_ES |
dc.subject | dosing | es_ES |
dc.subject | pharmacokinetics | es_ES |
dc.subject | pharmacodynamics | es_ES |
dc.subject | Monte Carlo simulation | es_ES |
dc.subject | augmented renal clearance | es_ES |
dc.subject | critically ill patient | es_ES |
dc.subject | neurocritical care | es_ES |
dc.title | Optimization of levetiracetam dosing regimen in critically ill patients with augmented renal clearance: a Monte Carlo simulation study | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | © The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://jintensivecare.biomedcentral.com/articles/10.1186/s40560-022-00611-w | es_ES |
dc.identifier.doi | 10.1186/s40560-022-00611-w | |
dc.departamentoes | Farmacia y ciencias de los alimentos | es_ES |
dc.departamentoeu | Farmazia eta elikagaien zientziak | es_ES |
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