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: Film-coated tablet: Levetiracetam is rapidly absorbed after oral administration. Oral absolute bioavailability is close to 100%. Peak plasma concentrations (C_max) are achieved at 1.3 hours after dosing. Steady-state is achieved after two days of a twice daily administration schedule. Peak concentration (C_max) are typically 31 and 43 μg/mL following a single 1,000 mg dose and repeated 1,000 mg twice daily dose, respectively.
The extent of absorption is dose-independent and is not altered by food.
Injection: 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.
Pharmacokinetics in special population: Geriatric patients 65 years of age and older: The greater frequency of decreased renal function observed in this age group, total body clearance was reduced by 38% and half-life was increased by 2.5 hours in geriatric patients with creatine clearances of 30-74 mL/minute.
Patients with hepatic impairment: Levetiracetam pharmacokinetics were unchanged in patients with mild (Child-Pugh Class A) to moderate (Child-Pugh Class B) hepatic impairment. Total body clearance was reduced by 50% in patients with severe hepatic impairment (Child-Pugh Class C), principally because of decreased renal clearance.
Patients with renal impairment: Clearance is decreased and half-life is increased.