Levisat Mechanism of Action

Pharmacotherapeutic group: Antiepileptics, other antiepileptics.
Therapeutic code: N03AX14.
Pharmacology: Pharmacodynamics: Mechanism of action: The active substance, levetiracetam, is a pyrrolidone derivative (S-enantiomer of α-ethyl-2-oxo 1-pyrrolidine acetamide), chemically unrelated to existing antiepileptic active substances.
The mechanism of action of levetiracetam still remains to be fully elucidated.
FC tab: Clinical efficacy and safety: Adjunctive therapy in the treatment of partial onset seizures with or without secondary generalization in adults, adolescents and children from 4 years of age with epilepsy.
Infusion conc: Pharmacodynamics effects: In man, an activity in both partial and generalized epilepsy conditions (epileptiform discharge/photo paroxysmal response) has confirmed the broad spectrum pharmacological profile of levetiracetam.
Pharmacokinetics: Levetiracetam is a highly soluble and permeable compound. The pharmacokinetic profile is linear with low intra- and inter-subject variability. There is no modification of the clearance after repeated administration.
Absorption: FC tab: 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. The extent of absorption is dose-independent and is not altered by food.
Distribution: Neither levetiracetam nor its primary metabolite are significantly bound to plasma proteins (<10%).
Infusion conc: The volume of distribution of levetiracetam is approximately 0.5 to 0.7 l/kg, a value close to total body water volume.
Metabolism: Levetiracetam is not extensively metabolized in humans. The major metabolic pathway (24% of the dose) is an enzymatic hydrolysis of the acetamide group. Production of the primary metabolite, UCB L057, is not supported by liver cytochrome P450 isoforms. Hydrolysis of the acetamide group was measurable in a large number of tissues including blood cells. The metabolite UCB L057 is pharmacologically inactive.
Elimination: Infusion conc: The plasma half-life in adults was 7±1 hours and did not vary either with dose, route of administration or repeated administration. The mean total body clearance was 0.96 ml/min/kg. It is therefore recommended to adjust the maintenance daily dose of levetiracetam, based on creatinine clearance in patients with moderate and severe renal impairment.
Renal impairment: The apparent body clearance of both Levetiracetam and of its primary metabolite is correlated to the creatinine clearance.