{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T11:19:21Z","timestamp":1773400761372,"version":"3.50.1"},"reference-count":32,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2006,7,19]],"date-time":"2006-07-19T00:00:00Z","timestamp":1153267200000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2006,7]]},"abstract":"<jats:p><jats:bold>Summary:\u2002<\/jats:bold>  <jats:italic>Purpose:<\/jats:italic> The primary objective of this placebo\u2010controlled study was to evaluate the safety and tolerability of levetiracetam (LEV) administered intravenously (IV) at higher doses and\/or at a faster infusion rate than proposed. The secondary objective was to assess LEV pharmacokinetics.<\/jats:p><jats:p> <jats:italic>Methods:<\/jats:italic> Single ascending doses of LEV administered by IV infusion (2,000, 3,000, 4,000 mg over 15 min; 1,500, 2,000, 2,500 mg over 5 min) were evaluated in 48 healthy subjects in a randomized, single\u2010blind, placebo\u2010controlled study.<\/jats:p><jats:p> <jats:italic>Results:<\/jats:italic> All randomized subjects completed the study. Adverse events reported after IV administration of LEV (\u22644,000 mg infused over 15 min and \u22642,500 mg infused over 5 min) were primarily related to the CNS (dizziness, 52.8%; somnolence, 33.3%; fatigue, 11.1%; headache, 8.3%) and were consistent with the established safety profile for the oral formulation. Safety profiles were similar for each dose level of LEV and for both IV infusion rates, with no clear relation noted between incidence of adverse events and IV dose level or infusion rate. The pharmacokinetics of LEV administered by IV infusion was comparable across all dose groups and infusion rates. Respective geometric means (coefficient of variation) for 4,000 mg administered over 15 min and 2,500 mg infused over 5 min were maximum plasma concentration, 145 (24.6%) and 94.3 (36.2%) \u03bcg\/ml; area under the plasma concentration\u2013time curve, 1,239 (19.2%) and 585 (9.6%) \u03bcg\/h\/ml; terminal half\u2010life, 8.0 (14.5%) and 7.0 (12.7%) h.<\/jats:p><jats:p> <jats:italic>Conclusions:<\/jats:italic> LEV administered by IV infusion at dosages and\/or infusion rates higher than those proposed was well tolerated in healthy subjects, and the pharmacokinetic profile was consistent with that for LEV administered orally.<\/jats:p>","DOI":"10.1111\/j.1528-1167.2006.00586.x","type":"journal-article","created":{"date-parts":[[2006,7,20]],"date-time":"2006-07-20T17:13:07Z","timestamp":1153415587000},"page":"1128-1135","source":"Crossref","is-referenced-by-count":150,"title":["Levetiracetam Intravenous Infusion: A Randomized, Placebo\u2010controlled Safety and Pharmacokinetic Study"],"prefix":"10.1111","volume":"47","author":[{"given":"Steven","family":"Ramael","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agn\u00e8s","family":"Daoust","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Otoul","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathalie","family":"Toublanc","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mona","family":"Troenaru","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhihong (Sarah)","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Armel","family":"Stockis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,7,19]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308208101"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1528-1157.2002.24501.x"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(01)01884-5"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200303030-00035"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.104.079327"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704766"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.55.2.236"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-1211(01)00323-0"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.2000.tb04605.x"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.2000.tb00323.x"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-1211(03)00080-9"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1059-1311(02)00292-3"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0013-9580.2005.31504.x"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-1211(02)00247-4"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.56.12.1772"},{"issue":"6","key":"e_1_2_5_17_2","first-page":"268","article-title":"Levetiracetam intravenous infusion: safety, tolerability and bioavailability versus oral tablet","volume":"46","author":"Ramael S","year":"2005","journal-title":"Epilepsia"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1528-1157.2003.25302.x"},{"key":"e_1_2_5_19_2","volume-title":"Proc\u2010StatXact 4 for SAS Users","author":"Meta C","year":"1999"},{"key":"e_1_2_5_20_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1026451721686"},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1517\/14740338.3.5.415"},{"key":"e_1_2_5_22_2","unstructured":"BaulacM VossG KrygierC et al. andthe LEV N01166 Study Group.Safety profile of levetiracetam intravenous infusion (1000\u20103000 mg\/d b.i.d. administration) in patients with partial\u2010onset seizures.Presented at American Epilepsy Society 2005 Annual Meeting; December 2\u20106 2005; Washington DC. 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