BACKGROUND AND 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.
RCT Entities:
BACKGROUND AND 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: Michel Baulac; Martin J Brodie; Christian E Elger; Karsten Krakow; Armel Stockis; Paul Meyvisch; Ursula Falter Journal: Epilepsia Date: 2007-02-22 Impact factor: 5.864