PURPOSE: The primary objective of this placebo-controlled 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. METHODS: 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-blind, placebo-controlled study. RESULTS: All randomized subjects completed the study. Adverse events reported after IV administration of LEV (<or=4,000 mg infused over 15 min and <or=2,500 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%) mug/ml; area under the plasma concentration-time curve, 1,239 (19.2%) and 585 (9.6%) mug/h/ml; terminal half-life, 8.0 (14.5%) and 7.0 (12.7%) h. CONCLUSIONS: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.
RCT Entities:
PURPOSE: The primary objective of this placebo-controlled 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. METHODS: 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-blind, placebo-controlled study. RESULTS: All randomized subjects completed the study. Adverse events reported after IV administration of LEV (<or=4,000 mg infused over 15 min and <or=2,500 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%) mug/ml; area under the plasma concentration-time curve, 1,239 (19.2%) and 585 (9.6%) mug/h/ml; terminal half-life, 8.0 (14.5%) and 7.0 (12.7%) h. CONCLUSIONS: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.
Authors: Pavel Klein; Daniel Herr; Phillip L Pearl; JoAnne Natale; Zachary Levine; Claude Nogay; Fabian Sandoval; Stacey Trzcinsky; Shireen M Atabaki; Tammy Tsuchida; John van den Anker; Steven J Soldin; Jianping He; Robert McCarter Journal: Epilepsy Behav Date: 2012-07-07 Impact factor: 2.937
Authors: Kristen E Jones; Ava M Puccio; Kathy J Harshman; Bonnie Falcione; Neal Benedict; Brian T Jankowitz; Martina Stippler; Michael Fischer; Erin K Sauber-Schatz; Anthony Fabio; Joseph M Darby; David O Okonkwo Journal: Neurosurg Focus Date: 2008-10 Impact factor: 4.047