title: Pharmacokinetics, Safety and Bioequivalence of Levetiracetam Intravenous Infusion and Oral Tablets in Healthy Chinese Subjects.
abstract: OBJECTIVE
  Levetiracetam is available in China as adjunctive oral therapy for partial-onset seizures. This study was conducted to evaluate the bioequivalence between single-dose intravenous infusion and oral levetiracetam 1500 mg (Part A), and to assess the pharmacokinetics of multiple-dose intravenous infusion at the same dose (Part B) in healthy Chinese subjects.
  
  
  METHODS
  Part A was an open-label, crossover comparison (intravenous vs. oral), while Part B was a double-blind, parallel-group study of intravenous levetiracetam versus intravenous placebo administered for 5 days.
  
  
  RESULTS
  Bioequivalence was demonstrated between the 45-min intravenous infusion and oral tablets, with geometric mean area under the plasma concentration-time curve (AUC) from time 0 to infinity (AUC(∞)) 492.3 and 506.8 μg·h/mL, and geometric mean maximum concentration (Cmax) 65.12 and 55.93 μg/mL for intravenous infusion and oral dosing, respectively. Linear pharmacokinetics were demonstrated (geometric least-squares mean AUC during the dosing interval τ at steady state (AUC(τ,ss)) 475.6 μg·h/mL; geometric least-squares mean AUC(∞) after single dose 501.7 μg·h/mL; linearity factor = 0.948). Geometric mean Cmax (77.44 μg/mL) and AUC(τ,ss) (475.6 μg·h/mL) of intravenous infusion levetiracetam 1500 mg after multiple doses were within the expected range, based on their respective single-dose values and the terminal half-life of levetiracetam after a single dose (7.13 h). A theoretical accumulation of approximately 40% would be expected after multiple doses, which is consistent with the calculated accumulation of 18.0 and 43.5% (Rmax and R(AUC), respectively).
  
  
  CONCLUSIONS
  Intravenous infusion of levetiracetam is bioequivalent to oral levetiracetam in healthy Chinese subjects and is a suitable alternative for levetiracetam administration in patients who are temporarily unable to take their medication orally.
authors.affiliation: UCB Pharma, Chemin du Foriest, 1420, Braine-l'Alleud, Belgium, Nathalie.Toublanc@ucb.com.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Toublanc
authors.forename: Xinlu
authors.initials: X
authors.lastname: Du
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.forename: Pritibha
authors.initials: P
authors.lastname: Singh
authors.forename: Robert
authors.initials: R
authors.lastname: Chan
authors.forename: Armel
authors.initials: A
authors.lastname: Stockis
mesh_terms: D000284:Administration, Oral; D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007262:Infusions, Intravenous; D000077287:Levetiracetam; D008297:Male; D010889:Piracetam / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D013607:Tablets; D013810:Therapeutic Equivalency
chemical_list: D013607:Tablets; D000077287:Levetiracetam; D010889:Piracetam