Summary:Purpose: The primary objective of this placebocontrolled 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 (≤4,000 mg infused over 15 min and ≤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%) μg/ml; area under the plasma concentration-time curve, 1,239 (19.2%) and 585 (9.6%) μg/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.

Overall, the results of this thorough QT study indicate that the methodology of the trial was valid and sensitive enough to demonstrate the absence of effect of levocetirizine at both therapeutic (5 mg) and supra-therapeutic (30 mg) doses on cardiac repolarisation.

BACKGROUND The primary objective was to evaluate the safety, tolerability and pharmacokinetics of levetiracetam (LEV) administered intravenously at a higher dose and/or faster infusion rate than recommended. METHODS Single ascending doses of LEV in 100 mL saline administered by intravenous (IV) infusion (2, 3, 4 g over 15 minutes; 1.5, 2, 2.5 g over 5 minutes) were evaluated in 48 healthy subjects in a randomised, single‐blind, placebo‐controlled study. RESULTS Adverse events (AEs) reported following IV administration of LEV (up to 4g infused over 15 minutes and up to 2.5g infused over 5 minutes) were primarily related to the central nervous system (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 relationship noted between incidence of AEs and IV dose level or infusion rate. The pharmacokinetics of LEV administered by IV infusion were comparable across all dose groups and infusion rates. CONCLUSIONS LEV administered by IV infusion at higher doses and/or faster rates than the current maximum recommendation (1.5 g in 15 minutes) was safe and well tolerated in healthy subjects, and the pharmacokinetic profile is consistent with that for LEV administered orally. Clinical Pharmacology & Therapeutics (2005) 79, P81–P81; doi: