Focale Mechanism of Action

Pharmacology: Pharmacodynamics: The precise mechanism(s) by which levetiracetam exerts its antiepileptic effect is unknown. The antiepileptic activity of levetiracetam was assessed in a number of animal models of epileptic seizures.
In vitro and in vivo recordings of epileptiform activity from the hippocampus have shown that levetiracetam inhibits burst firing without affecting normal neuronal excitability, suggesting that levetiracetam may selectively prevent hypersynchronization of epileptiform burst firing and propagation of seizure activity.
Pharmacokinetics: Absorption: N/A (Intravenous injection).
Distribution: Levetiracetam and its major metabolite are less than 10% bound to plasma proteins. The volume of distribution of levetiracetam is 0.7 L/kg, close to volume of intracellular and extracellular water.
Metabolism: Levetiracetam is not extensively metabolized in humans. The major metabolic pathway is the enzymatic hydrolysis of the acetamide group. Cytochrome P450 isoenzyme system is not involved in the metabolism of levetiracetam. Levetiracetam and its major metabolite are neither inhibitors of or substrates for cytochrome P450 isoforms, epoxide hydrolase, or UDP-glucuronidation enzymes.
Excretion: Levetiracetam plasma half-life in adults is 7±1 hour and is unaffected by dose, route of administration, or repeated administration. Levetiracetam is eliminated from the systemic circulation as unchanged drug by renal excretion (66% of the dose). The total body clearance is 0.96 mL/min/kg, and the renal clearance 0.6 mL/min/kg. The mechanism of excretion is glomerular filtration with subsequent partial tubular reabsorption. The metabolite ucb L057 is excreted by glomerular filtration and active tubular secretion, with a renal clearance of 4 mL/min/kg. Levetiracetam clearance and elimination is correlated to CrCl.