{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T03:27:00Z","timestamp":1788319620998,"version":"build-2803163510"},"reference-count":11,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T00:00:00Z","timestamp":1645574400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate the pharmacokinetics, safety, and tolerability of brivaracetam (BRV) as 15\u2010min intravenous (IV) infusion and bolus (\u22642\u2010min injection).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>EP0065 (ClinicalTrials.gov: NCT03405714) was a Phase 2, multicenter, open\u2010label trial in patients \u22651\u00a0month to &lt;16\u00a0years of age with epilepsy. Patients received up to 5\u00a0mg\/kg\/day BRV (not exceeding 200\u00a0mg\/day). Enrollment was sequential by descending age, depending on safety review. Outcomes included BRV plasma concentrations before and after IV administration, treatment\u2010emergent adverse events (TEAEs), and discontinuations due to TEAEs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fifty patients were enrolled, received BRV, and completed the trial. Twenty\u2010six patients (52.0%) received 15\u2010min infusions and 24 (48.0%) received bolus injections. Most patients (80.0%) received one IV dose. In the 15\u2010min infusion group, geometric mean (GeoMean) BRV concentrations 15 (\u00b12)\u00a0min (<jats:italic>n<\/jats:italic>\u00a0=\u00a021) and 3\u00a0h (\u00b115\u00a0min) (<jats:italic>n<\/jats:italic>\u00a0=\u00a021) post dose were 1903.0\u00a0ng\/mL (geometric coefficient of variation [GeoCV]: 60.7%) and 1130.3\u00a0ng\/mL (58.8%), respectively. In the bolus group, GeoMean BRV concentrations 15 (\u00b12)\u00a0min (<jats:italic>n<\/jats:italic>\u00a0=\u00a019) and 3\u00a0h (\u00b115\u00a0min) (<jats:italic>n<\/jats:italic>\u00a0=\u00a021) post dose were 1704.8\u00a0ng\/mL (GeoCV: 74.5%) and 1383.9\u00a0ng\/mL (85.0%), respectively. Overall, 14 patients (28.0%) had TEAEs (15\u2010min infusion: 8 [30.8%]; bolus: 6 [25.0%]), most commonly (\u22655% of patients) somnolence (3\u00a0[6.0%]). Ten patients (20.0%) had drug\u2010related TEAEs (15\u2010min infusion: 6 [23.1%]; bolus:\u00a04\u00a0[16.7%]). No patients discontinued due to TEAEs, and no deaths occurred.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>IV BRV (up to 200\u00a0mg\/day) was well tolerated in patients \u22651\u00a0month to &lt;16\u00a0years of age, regardless of whether BRV was administered as 15\u2010min infusion or bolus. No unexpected safety or pharmacokinetic differences were observed between patients receiving 15\u2010min infusions or bolus, and plasma concentrations were in the expected range. Safety results were consistent with the known safety profile of oral BRV, with no new safety concerns identified.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.17187","type":"journal-article","created":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T17:26:55Z","timestamp":1645637215000},"page":"855-864","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Pharmacokinetics, safety, and tolerability of intravenous brivaracetam in pediatric patients with epilepsy: An open\u2010label trial"],"prefix":"10.1111","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6016-2883","authenticated-orcid":false,"given":"Mark Kristof","family":"Farkas","sequence":"first","affiliation":[{"name":"First Department of Pediatrics Semmelweis University  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harriet","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Neurology Icahn School of Medicine at Mount Sinai Hospital  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andras","family":"Fogarasi","sequence":"additional","affiliation":[{"name":"Child Neurology Department Bethesda Children\u2019s Hospital  Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Bozorg","sequence":"additional","affiliation":[{"name":"UCB Pharma  Morrisville North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gareth D.","family":"James","sequence":"additional","affiliation":[{"name":"Medical Statistics Consultancy Ltd  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Krauwinkel","sequence":"additional","affiliation":[{"name":"UCB Pharma  Braine\u2010l\u2019Alleud Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Morita","sequence":"additional","affiliation":[{"name":"UCB Pharma  Morrisville North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar","family":"Will","sequence":"additional","affiliation":[{"name":"UCB Pharma  Monheim am Rhein Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan\u2010Peer","family":"Elshoff","sequence":"additional","affiliation":[{"name":"UCB Pharma  Monheim am Rhein Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,2,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1684\/epd.2015.0736"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13859"},{"key":"e_1_2_10_4_1","volume-title":"Briviact\u00ae (brivaracetam) summary of product characteristics","author":"UCB Pharma S.A","year":"2020"},{"key":"e_1_2_10_5_1","unstructured":"Briviact\u00ae(brivaracetam) prescribing information. UCB Inc. 2021. Available at:https:\/\/www.briviact.com\/briviact\u2010PI.pdfAccessed September 16 2021"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40272-019-00332-y"},{"key":"e_1_2_10_7_1","first-page":"438","article-title":"Bioavailability and safety of the intravenous administration of brivaracetam","volume":"49","author":"Hulhoven R","year":"2008","journal-title":"Epilepsia"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13433"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.275"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2019.106864"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2019.11.007"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.761"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.17187","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/epi.17187","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.17187","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T03:13:15Z","timestamp":1692846795000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.17187"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,23]]},"references-count":11,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,4]]}},"alternative-id":["10.1111\/epi.17187"],"URL":"https:\/\/doi.org\/10.1111\/epi.17187","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,23]]},"assertion":[{"value":"2021-11-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}