title: Development of lacosamide for the treatment of partial-onset seizures.
abstract: Lacosamide is an antiepileptic drug (AED) available in multiple formulations that was first approved in 2008 as adjunctive therapy for partial-onset seizures (POS) in adults. Unlike traditional sodium channel blockers affecting fast inactivation, lacosamide selectively enhances sodium channel slow inactivation. This mechanism of action results in stabilization of hyperexcitable neuronal membranes, inhibition of neuronal firing, and reduction in long-term channel availability without affecting physiological function. Lacosamide has a well-characterized and favorable pharmacokinetic profile, including a fast absorption rate, minimal or no interaction with cytochrome P-450 izoenzymes, and a low potential for drug-drug interactions. Lacosamide clinical development included three placebo-controlled, double-blind, randomized trials conducted in more than 1300 patients, each demonstrating safety and efficacy of lacosamide compared to placebo as adjunctive therapy for adults with POS. The clinical use of lacosamide may broaden, pending results of trials evaluating its use as monotherapy for POS in adults, as treatment for epilepsy in pediatric subjects, and as adjunctive treatment for uncontrolled primary generalized tonic-clonic seizures in those with idiopathic generalized epilepsy.
authors.affiliation: UCB Pharma, Raleigh, North Carolina 27617, USA. pamela.doty@ucb.com
authors.forename: Pamela
authors.initials: P
authors.lastname: Doty
authors.forename: David
authors.initials: D
authors.lastname: Hebert
authors.forename: Francois-Xavier
authors.initials: FX
authors.lastname: Mathy
authors.forename: William
authors.initials: W
authors.lastname: Byrnes
authors.forename: James
authors.initials: J
authors.lastname: Zackheim
authors.forename: Kelly
authors.initials: K
authors.lastname: Simontacchi
mesh_terms: D000081:Acetamides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D000927:Anticonvulsants / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004828:Epilepsies, Partial / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D000078334:Lacosamide; D016032:Randomized Controlled Trials as Topic / Q000379:methods / Q000639:trends; D016896:Treatment Outcome
chemical_list: D000081:Acetamides; D000927:Anticonvulsants; D000078334:Lacosamide
keywords: antiepileptic drug; epilepsy; lacosamide; partial-onset seizures