Title
Fluctuating and constant valproate administration gives equivalent seizure control in rats with genetic and acquired epilepsy Fluctuating and constant valproate administration gives equivalent seizure control in rats with genetic and acquired epilepsy
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
London ,
Subject
Human medicine
Source (journal)
Seizure: European journal of epilepsy. - London
Volume/pages
20(2011) :1 , p. 72-79
ISSN
1059-1311
ISI
000286866100013
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Purpose: Controlled-release formulations of Valproate (VPA) reduce side effects by minimizing peak plasma VPA concentrations in patients with epilepsy. However, the impact of this on anti-seizure efficacy has not been thoroughly explored. Here the pharmacokinetics and pharmacodynamics of chronic intermittent (consequently, peak VPA concentrations) and continuous VPA administration were directly compared in two rat models of epilepsy. Methods: Genetic Absence Epilepsy Rats from Strasbourg (GAERS) received a single acute bolus of VPA (100 mg/kg intravenously) combined with electroencephalography (EEG) and/or blood sampling for 180 min post-injection. GAERS and epileptic rats post-kainic acid-induced status epilepticus were chronically infused intravenously (3-5 days, respectively) with (i) saline followed by in random order (ii) intermittent and (iii) continuous VPA (42 mg/kg/h), separated by two days of wash-out. Seizures were quantified using video-EEG monitoring and VPA levels measured in brain, cerebrospinal fluid and plasma. Results: Following acute VPA administration seizure suppression in GAERS persisted after plasma VPA levels became very low. Chronic intermittent and continuous VPA significantly suppressed seizures in both models (p < 0.01) with no difference between administration regimens. In GAERS, the pattern of seizure suppression during intermittent treatment was constant, in contrast to the fluctuating VPA plasma and brain levels. There was discordance between the temporal pattern of plasma, brain VPA levels and seizure suppression efficacy in GAERS. Conclusion: Administration regimes that result in fluctuating VPA blood levels achieve equivalent sustained seizure suppression as those that maintain steady mid-range concentrations. (C) 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Full text (open access)
https://repository.uantwerpen.be/docman/irua/804053/c547482b.pdf
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