An Open-label, Bioequivalence Study to Evaluate LEV Administered as a 45-min Intravenous Infusion and Same Dosage LEV Oral Tablet in Chinese

• Area under the plasma drug concentration versus time curve from hour 0 to the time with a last quantifiable concentration (AUC(0-t)) [ Time Frame: Pharmacokinetic samples were taken from pre-dose to 36 hours after Levetiracetam administration ] [ Designated as safety issue: No ]
• Area under the plasma drug concentration-time curve from 0 to infinity (AUC) [ Time Frame: Pharmacokinetic samples were taken from pre-dose to 36 hours after Levetiracetam administration ] [ Designated as safety issue: No ]
  The area under the curve extrapolated to infinity is calculated as the sum of AUC(0-t) and a residual part extrapolated to infinite time.
• Maximum measured plasma concentration (Cmax) [ Time Frame: Pharmacokinetic samples were taken from pre-dose to 36 hours after Levetiracetam administration ] [ Designated as safety issue: No ]
  The value of the maximum plasma concentration is directly obtained from the observed plasma concentration versus time curves.

• Area under the plasma drug concentration-time curve calculated from 0 to 12 h (AUC(0-12)) [ Time Frame: Pharmacokinetic samples were taken from pre-dose to 36 hours after Levetiracetam administration ] [ Designated as safety issue: No ]
• Plasma concentration at the end of the 45-minutes intravenous (iv) infusion (C45'(iv)) [ Time Frame: Pharmacokinetic samples were taken at 45 min after Levetiracetam administration ] [ Designated as safety issue: No ]
  The value of the plasma concentration at the end of the 45-min iv infusion is directly obtained from the experimental data of plasma concentration versus time curves.
• Time to reach the maximum plasma concentration of Levetiracetam after administration (tmax) [ Time Frame: Pharmacokinetic samples were taken from pre-dose to 36 hours after Levetiracetam administration ] [ Designated as safety issue: No ]
• Terminal half-life of Levetiracetam (t1/2) [ Time Frame: Pharmacokinetic samples were taken from pre-dose to 36 hours after Levetiracetam administration ] [ Designated as safety issue: No ]
  The terminal half-life associated with the terminal rate constant λ_z is calculated as: ln2/λ_z. λ_z is the first order rate constant of elimination.
• Total body clearance after intravenous infusion of Levetiracetam (CL(iv)) [ Time Frame: Pharmacokinetic samples were taken from pre-dose to 36 hours after Levetiracetam administration ] [ Designated as safety issue: No ]

  The CL(iv) is calculated as:

  CL=Dose of LEV/AUC.

• Apparent total body clearance after oral administration of Levetiracetam (CL/F(tablet)) [ Time Frame: Pharmacokinetic samples were taken from pre-dose to 36 hours after Levetiracetam administration ] [ Designated as safety issue: No ]

  The CL/F (tablet) is calculated as:

  CL/F=Dose of LEV/AUC.

• Volume of distribution after intravenous infusion of Levetiracetam (Vz(iv)) [ Time Frame: Pharmacokinetic samples were taken from pre-dose to 36 hours after Levetiracetam administration ] [ Designated as safety issue: No ]

  The volume of distribution after iv infusion is calculated as:

  Vz=CL/λ_z, where CL is the total body clearance and λ_z the first order rate constant of elimination.

• Apparent volume of distribution after oral administration of Levetiracetam (Vz/F(tablet)) [ Time Frame: Pharmacokinetic samples were taken from pre-dose to 36 hours after Levetiracetam administration ] [ Designated as safety issue: No ]

  The apparent volume of distribution after oral administration is calculated as:

  Vz/F= (CL/F)/λ_z.

The part A of N01362 is to evaluate the bioequivalence of Levetiracetam (LEV) 1500 mg intravenous (iv) infusion when compared to tablet oral administration in Chinese healthy volunteers.

The study includes 2 parts, part A is to evaluate the bioequivalence of Levetiracetam (LEV) 1500 mg intravenous (iv) infusion when compared to oral tablet, part B is to assess pharmacokinetic profile of LEV infusion during repeated dosing in Chinese healthy volunteers.

• Drug: Levetiracetam
  Levetiracetam 1.500 mg (500 mg/ 5 mL vials) administered as a 45 minutes intravenous infusion diluted in 100 mL 0.9 % saline solution in the morning of Day 1.
  Other Name: Keppra
• Drug: Levetiracetam
  Levetiracetam single oral administration of 3 tablets of 500 mg immediate release tablet.
  Other Name: Keppra

• Experimental: Levetiracetam iv infusion
  Levetiracetam intravenous (iv) 45 min infusion administered as one single dose.
  Intervention: Drug: Levetiracetam
• Experimental: Levetiracetam oral tablet
  Levetiracetam oral tablet administered as one single dose.
  Intervention: Drug: Levetiracetam

Inclusion Criteria:

• Chinese, age 18-40, weight ≥ 50 kg
• Healthy volunteers with normal vital signs, good physical and mental health status and normal electrocardiogram and laboratory test

Exclusion Criteria:

• History or presence of each systems disorders capable of altering the absorption, metabolism or elimination of drugs, or of constituting a risk factor when taking the study medication
• History or presence of drug addiction or excessive use of alcohol
• Symptomatic or asymptomatic Orthostatic Hypotension at screening
• Current smokers and former smokers
• Heavy caffeine drinker
• History of frequent and severe headache
• Any drug treatment
• Subjects who are known to have Serum Hepatitis or who are carriers of the Hepatitis B surface antigen, or Hepatitis C antibody or who are HIV positive
• Subjects on a controlled sodium diet
• Subject has made a blood donation or had a comparable blood loss