{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T14:52:53Z","timestamp":1789397573327,"version":"build-2803163510"},"reference-count":17,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2007,1,12]],"date-time":"2007-01-12T00:00:00Z","timestamp":1168560000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2007,6]]},"abstract":"<jats:sec><jats:label\/><jats:p> <jats:bold>What is already known about this subject<\/jats:bold> <\/jats:p><jats:p>\u2022\u2002Brivaracetam is a new chemical entity structurally related to levetiracetam, displaying a markedly higher affinity for the binding site believed to be primarily involved in the antiepileptic effect of levetiracetam.<\/jats:p><jats:p>\u2022\u2002Studies to evaluate the pharmacological profile of brivaracetam demonstrate an approximately 10\u2010fold higher potency than levetiracetam as well as a higher efficacy in models of epilepsy.<\/jats:p><jats:p>\u2022\u2002If translated into therapeutic effects in humans, this would mean a greater decrease in seizure frequency and a higher number of responders and seizure\u2010free patients in refractory epileptic patients as seen with levetiracetam.<\/jats:p><jats:p> <jats:bold>What this study adds<\/jats:bold> <\/jats:p><jats:p>\u2022\u2002This article reports the results of the first in human study with brivaracetam. Its pharmacokinetics and adverse events profile after single administration are evaluated, together with the effect of food on the former.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Healthy males (<jats:italic>n<\/jats:italic>\u2003=\u200327, divided into three alternating panels of nine subjects) received two different single oral doses of brivaracetam (10\u20131400\u2003mg) and one dose of placebo during three periods of a randomized, double\u2010blind, placebo\u2010controlled study. The effect of food on its pharmacokinetics was assessed using a standard two\u2010way crossover design in a further eight subjects who received two single oral doses of brivaracetam (150\u2003mg) in the fasting state and after a high fat meal.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Adverse events, none of which were serious, were mostly CNS\u2010related and included somnolence, dizziness, and decreased attention, alertness, and motor control. Their incidence, severity and duration were dose\u2010related. The maximum tolerated dose was established to be 1000\u2003mg. Severe somnolence lasting 1 day occurred in one subject following 1400\u2003mg. Brivaracetam was rapidly absorbed under fasting conditions, with a median <jats:italic>t<\/jats:italic><jats:sub><jats:italic>max<\/jats:italic><\/jats:sub> of approximately 1\u2003h. <jats:italic>C<\/jats:italic><jats:sub><jats:italic>max<\/jats:italic><\/jats:sub> was dose\u2010proportional from 10 to1400\u2003mg, whereas AUC deviated from dose linearity above 600\u2003mg. A high\u2010fat meal had no effect on AUC (point estimate 0.99, 90%CI: 0.92\u20131.07) but delayed <jats:italic>t<\/jats:italic><jats:sub><jats:italic>max<\/jats:italic><\/jats:sub> (3\u2003h) and decreased <jats:italic>C<\/jats:italic><jats:sub><jats:italic>max<\/jats:italic><\/jats:sub> (point estimate 0.72, 90%CI: 0.66\u20130.79).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1365-2125.2006.02829.x","type":"journal-article","created":{"date-parts":[[2007,1,12]],"date-time":"2007-01-12T13:24:01Z","timestamp":1168608241000},"page":"680-688","source":"Crossref","is-referenced-by-count":101,"title":["The pharmacokinetics, CNS pharmacodynamics and adverse event profile of brivaracetam after single increasing oral doses in healthy males"],"prefix":"10.1111","volume":"63","author":[{"given":"Maria 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