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Polymorphisms Affecting the Response to Novel Antiepileptic Drugs

Epilepsy is one of the most frequent chronic neurologic disorders that affects nearly 1% of the population worldwide, especially in developing countries. Currently, several antiepileptic drugs (AEDs) are available for its therapy, and although the prognosis is good for most patients, 20%–30% amongst...

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Autores principales: Urzì Brancati, Valentina, Pinto Vraca, Tiziana, Minutoli, Letteria, Pallio, Giovanni
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917302/
https://www.ncbi.nlm.nih.gov/pubmed/36768858
http://dx.doi.org/10.3390/ijms24032535
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author Urzì Brancati, Valentina
Pinto Vraca, Tiziana
Minutoli, Letteria
Pallio, Giovanni
author_facet Urzì Brancati, Valentina
Pinto Vraca, Tiziana
Minutoli, Letteria
Pallio, Giovanni
author_sort Urzì Brancati, Valentina
collection PubMed
description Epilepsy is one of the most frequent chronic neurologic disorders that affects nearly 1% of the population worldwide, especially in developing countries. Currently, several antiepileptic drugs (AEDs) are available for its therapy, and although the prognosis is good for most patients, 20%–30% amongst them do not reach seizure freedom. Numerous factors may explain AED-resistance such as sex, age, ethnicity, type of seizure, early epilepsy onset, suboptimal dosing, poor drug compliance, alcohol abuse, and in particular, genetic factors. Specifically, the interindividual differences in drug response can be caused by single nucleotide polymorphisms (SNPs) in genes encoding for drug efflux transporters, for the brain targets of AEDs, and for enzymes involved in drug metabolism. In this review, we used the PubMed database to retrieve studies that assessed the influence of SNPs on the pharmacokinetic (PK), pharmacodynamic (PD), and efficacy of new antiepileptic drugs. Our results showed that polymorphisms in the ABCB1, ABCC2, UGT1A4, UGT2B7, UGT2B15, CYP2C9, and CYP2C19 genes have an influence on the PK and efficacy of AEDs, suggesting that a genetic pre-evaluation of epileptic patients could help clinicians in prescribing a personalized treatment to improve the efficacy and the safety of the therapy.
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spelling pubmed-99173022023-02-11 Polymorphisms Affecting the Response to Novel Antiepileptic Drugs Urzì Brancati, Valentina Pinto Vraca, Tiziana Minutoli, Letteria Pallio, Giovanni Int J Mol Sci Review Epilepsy is one of the most frequent chronic neurologic disorders that affects nearly 1% of the population worldwide, especially in developing countries. Currently, several antiepileptic drugs (AEDs) are available for its therapy, and although the prognosis is good for most patients, 20%–30% amongst them do not reach seizure freedom. Numerous factors may explain AED-resistance such as sex, age, ethnicity, type of seizure, early epilepsy onset, suboptimal dosing, poor drug compliance, alcohol abuse, and in particular, genetic factors. Specifically, the interindividual differences in drug response can be caused by single nucleotide polymorphisms (SNPs) in genes encoding for drug efflux transporters, for the brain targets of AEDs, and for enzymes involved in drug metabolism. In this review, we used the PubMed database to retrieve studies that assessed the influence of SNPs on the pharmacokinetic (PK), pharmacodynamic (PD), and efficacy of new antiepileptic drugs. Our results showed that polymorphisms in the ABCB1, ABCC2, UGT1A4, UGT2B7, UGT2B15, CYP2C9, and CYP2C19 genes have an influence on the PK and efficacy of AEDs, suggesting that a genetic pre-evaluation of epileptic patients could help clinicians in prescribing a personalized treatment to improve the efficacy and the safety of the therapy. MDPI 2023-01-28 /pmc/articles/PMC9917302/ /pubmed/36768858 http://dx.doi.org/10.3390/ijms24032535 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Urzì Brancati, Valentina
Pinto Vraca, Tiziana
Minutoli, Letteria
Pallio, Giovanni
Polymorphisms Affecting the Response to Novel Antiepileptic Drugs
title Polymorphisms Affecting the Response to Novel Antiepileptic Drugs
title_full Polymorphisms Affecting the Response to Novel Antiepileptic Drugs
title_fullStr Polymorphisms Affecting the Response to Novel Antiepileptic Drugs
title_full_unstemmed Polymorphisms Affecting the Response to Novel Antiepileptic Drugs
title_short Polymorphisms Affecting the Response to Novel Antiepileptic Drugs
title_sort polymorphisms affecting the response to novel antiepileptic drugs
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917302/
https://www.ncbi.nlm.nih.gov/pubmed/36768858
http://dx.doi.org/10.3390/ijms24032535
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