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https://hdl.handle.net/2440/44040
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Type: | Journal article |
Title: | The pharmacokinetics, CNS pharmacodynamics and adverse event profile of brivaracetam after single increasing oral doses in healthy males |
Author: | Sargentini-Maier, M. Rolan, P. Connell, J. Tytgat, D. Jacobs, T. Pigeolet, E. Riethuisen, J. Stockis, A. |
Citation: | British Journal of Clinical Pharmacology, 2007; 63(6):680-688 |
Publisher: | Blackwell Publishing Ltd |
Issue Date: | 2007 |
ISSN: | 0306-5251 1365-2125 |
Statement of Responsibility: | Maria Laura Sargentini-Maier, Paul Rolan, John Connell, Dominique Tytgat, Tom Jacobs, Etienne Pigeolet, Jean-Michel Riethuisen & Armel Stockis |
Abstract: | <h4>Aims</h4>The objective of the study was to evaluate the pharmacokinetics (and how they are affected by food), CNS pharmacodynamics and the adverse event profile of brivaracetam after single increasing doses.<h4>Methods</h4>Healthy males (n = 27, divided into three alternating panels of nine subjects) received two different single oral doses of brivaracetam (10-1400 mg) and one dose of placebo during three periods of a randomized, double-blind, placebo-controlled study. The effect of food on its pharmacokinetics was assessed using a standard two-way crossover design in a further eight subjects who received two single oral doses of brivaracetam (150 mg) in the fasting state and after a high fat meal.<h4>Results</h4>Adverse events, none of which were serious, were mostly CNS-related and included somnolence, dizziness, and decreased attention, alertness, and motor control. Their incidence, severity and duration were dose-related. The maximum tolerated dose was established to be 1000 mg. Severe somnolence lasting 1 day occurred in one subject following 1400 mg. Brivaracetam was rapidly absorbed under fasting conditions, with a median t(max) of approximately 1 h. C(max) was dose-proportional from 10 to 1400 mg, whereas AUC deviated from dose linearity above 600 mg. A high-fat meal had no effect on AUC (point estimate 0.99, 90%CI: 0.92-1.07) but delayed t(max) (3 h) and decreased C(max) (point estimate 0.72, 90%CI: 0.66-0.79).<h4>Conclusions</h4>Brivaracetam was well tolerated after increasing single doses that represent up to several times the expected therapeutic dose. Brivaracetam was found to have desirable pharmacokinetic properties. The most common adverse events were somnolence and dizziness. |
Keywords: | Humans Epilepsy Pyrrolidinones Anticonvulsants Administration, Oral Double-Blind Method Dose-Response Relationship, Drug Adolescent Adult Middle Aged Male |
Description: | The definitive version is available at www.blackwell-synergy.com |
DOI: | 10.1111/j.1365-2125.2006.02829.x |
Published version: | http://dx.doi.org/10.1111/j.1365-2125.2006.02829.x |
Appears in Collections: | Aurora harvest 6 Pharmacology publications |
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