Rufinamide

Absorption

The oral suspension and tablet are bioequivalent on a mg per mg basis. Rufinamide is well absorbed but the rate is slow and the extent of absorption decreases as dose is increases. Based on urinary excretion, the extent of absorption was at least 85% following oral administration of a single dose of 600 mg rufinamide tablet under fed conditions. Bioavailability= 70%-85% (decreases with increasing doses); Tmax, fed and fasted states= 4-6 hours; Cmax, 10 mg/kg/day= 4.01 μL/mL; Cmax, 30mg/kg/day= 8.68 μL/mL; AUC (0h-12h), 10mg/kg/day= 37.8±47 μg·h/mL; AUC (0h-12h), 30mg/kg/day= 89.3±59 μg·h/mL.

Toxicity

The most commonly observed adverse reactions (≥10% and greater than placebo) were headache, dizziness, fatigue, somnolence, and nausea.

Description

Approximately 2.5 million people worldwide are afflicted with epilepsy, a devastating neurological disorder diagnosed by the tendency toward recurrent, unprovoked seizures, often of unknown etiology. Rufinamide has been launched primarily as adjunctive therapy of LGS. Its proposed mechanism of action involves the limitation of firing of sodium-dependent action potentials. The ultimate result is membrane stabilization. Since it does not exhibit measurable binding to monoamine, acetylcholine, histamine, glycine, AMPA/kainate, NMDA, or GABA receptors or systems, these receptor-mediated pathways are not anticipated to be involved in the exertion of rufinamide’s effects. Rufinamide displayed efficacy in several electrical and chemical animal seizure models.

The Uses of Rufinamide

Labelled Rufinamide (R701552). Antiepileptic triazole derivative which decreases firing by neurons at sodium channels. Anticonvulsant.

Indications

Adjunct therapy for treatment of seizures associated with Lennox-Gastaut syndrome.

Background

Rufinamide is a triazole derivative and an anticonvulsant medication to treat seizure disorders like Lennox-Gastuat syndrome, a form of childhood epilepsy. Clinical trials suggest its efficacy in the treatment of partial seizures.

What are the applications of Application

Rufinamide is a sodium channel protein inhibitor

Pharmacokinetics

At high concentrations will inhibit action of mGluR5 subtype receptors thus preventing the production of glutamate.

Metabolism

Rufinamide is extensively metabolized but has no active metabolites. Metabolism by carboxyesterases into inactive metabolite CGP 47292, a carboxylic acid derivative, via hydrolysis is the primary biotransformation pathway. A few minor additional metabolites were detected in urine, which appeared to be acyl-glucuronides of CGP 47292. The cytochrome P450 enzyme system or glutathiones are not involved with the metabolism of rufinamide. Rufinamide is a weak inhibitor of CYP 2E1. Rufinamide is a weak inducer of CYP 3A4 enzymes.