Cargando…
The Impact of Levetiracetam and Valproate on Platelet Functions—A Double-Blind, Placebo-Controlled Crossover Study
It is known that valproate inhibits platelet functions; however, the exact mechanisms are not clearly identified. We studied 12 healthy adult volunteers (1 female, 11 male; age range 31.7 ± 7.8 years) before and after valproate 500 mg and compared the results to levetiracetam 1000 mg as a control su...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917486/ https://www.ncbi.nlm.nih.gov/pubmed/36769581 http://dx.doi.org/10.3390/jcm12030933 |
_version_ | 1784886378210787328 |
---|---|
author | Olaizola, Itziar Brodde, Martin F. Kehrel, Beate E. Evers, Stefan |
author_facet | Olaizola, Itziar Brodde, Martin F. Kehrel, Beate E. Evers, Stefan |
author_sort | Olaizola, Itziar |
collection | PubMed |
description | It is known that valproate inhibits platelet functions; however, the exact mechanisms are not clearly identified. We studied 12 healthy adult volunteers (1 female, 11 male; age range 31.7 ± 7.8 years) before and after valproate 500 mg and compared the results to levetiracetam 1000 mg as a control substance and placebo. The study had a crossover and double-blind design. A blood sample was taken before and 90 min after medication intake, because the times to maximum serum concentration (T(max)) are 1.5 h for levetiracetam and 1 to 3 h for valproate. We analysed changes in platelet, erythrocyte, and leukocyte cell count and in platelet functions (CD62 expression (P selectin), thrombin binding, and fibrinogen binding). We found no significant differences in all cell counts before and after different study drugs. After valproate intake, but not after placebo or levetiracetam intake, the fibrinogen binding significantly decreased and the CD62 expression significantly increased resulting in decreased platelet aggregation. Our data suggest that the platelet dysfunctions reported for valproate result from decreased fibrinogen binding and from increased CD62 expression. This phenomenon might be one reason for the increased bleeding risk under valproate and cannot be observed for levetiracetam. |
format | Online Article Text |
id | pubmed-9917486 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99174862023-02-11 The Impact of Levetiracetam and Valproate on Platelet Functions—A Double-Blind, Placebo-Controlled Crossover Study Olaizola, Itziar Brodde, Martin F. Kehrel, Beate E. Evers, Stefan J Clin Med Article It is known that valproate inhibits platelet functions; however, the exact mechanisms are not clearly identified. We studied 12 healthy adult volunteers (1 female, 11 male; age range 31.7 ± 7.8 years) before and after valproate 500 mg and compared the results to levetiracetam 1000 mg as a control substance and placebo. The study had a crossover and double-blind design. A blood sample was taken before and 90 min after medication intake, because the times to maximum serum concentration (T(max)) are 1.5 h for levetiracetam and 1 to 3 h for valproate. We analysed changes in platelet, erythrocyte, and leukocyte cell count and in platelet functions (CD62 expression (P selectin), thrombin binding, and fibrinogen binding). We found no significant differences in all cell counts before and after different study drugs. After valproate intake, but not after placebo or levetiracetam intake, the fibrinogen binding significantly decreased and the CD62 expression significantly increased resulting in decreased platelet aggregation. Our data suggest that the platelet dysfunctions reported for valproate result from decreased fibrinogen binding and from increased CD62 expression. This phenomenon might be one reason for the increased bleeding risk under valproate and cannot be observed for levetiracetam. MDPI 2023-01-25 /pmc/articles/PMC9917486/ /pubmed/36769581 http://dx.doi.org/10.3390/jcm12030933 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 | Article Olaizola, Itziar Brodde, Martin F. Kehrel, Beate E. Evers, Stefan The Impact of Levetiracetam and Valproate on Platelet Functions—A Double-Blind, Placebo-Controlled Crossover Study |
title | The Impact of Levetiracetam and Valproate on Platelet Functions—A Double-Blind, Placebo-Controlled Crossover Study |
title_full | The Impact of Levetiracetam and Valproate on Platelet Functions—A Double-Blind, Placebo-Controlled Crossover Study |
title_fullStr | The Impact of Levetiracetam and Valproate on Platelet Functions—A Double-Blind, Placebo-Controlled Crossover Study |
title_full_unstemmed | The Impact of Levetiracetam and Valproate on Platelet Functions—A Double-Blind, Placebo-Controlled Crossover Study |
title_short | The Impact of Levetiracetam and Valproate on Platelet Functions—A Double-Blind, Placebo-Controlled Crossover Study |
title_sort | impact of levetiracetam and valproate on platelet functions—a double-blind, placebo-controlled crossover study |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917486/ https://www.ncbi.nlm.nih.gov/pubmed/36769581 http://dx.doi.org/10.3390/jcm12030933 |
work_keys_str_mv | AT olaizolaitziar theimpactoflevetiracetamandvalproateonplateletfunctionsadoubleblindplacebocontrolledcrossoverstudy AT broddemartinf theimpactoflevetiracetamandvalproateonplateletfunctionsadoubleblindplacebocontrolledcrossoverstudy AT kehrelbeatee theimpactoflevetiracetamandvalproateonplateletfunctionsadoubleblindplacebocontrolledcrossoverstudy AT eversstefan theimpactoflevetiracetamandvalproateonplateletfunctionsadoubleblindplacebocontrolledcrossoverstudy AT olaizolaitziar impactoflevetiracetamandvalproateonplateletfunctionsadoubleblindplacebocontrolledcrossoverstudy AT broddemartinf impactoflevetiracetamandvalproateonplateletfunctionsadoubleblindplacebocontrolledcrossoverstudy AT kehrelbeatee impactoflevetiracetamandvalproateonplateletfunctionsadoubleblindplacebocontrolledcrossoverstudy AT eversstefan impactoflevetiracetamandvalproateonplateletfunctionsadoubleblindplacebocontrolledcrossoverstudy |