Carisbamate (RWJ-333369)

Carisbamate ( RWJ-333369) is a novel neuromodulator, initially developed by SK Biopharmaceuticals ( Fairlawn, NJ), under development by Johnson & Johnson Pharmaceutical Research and Development ( La Jolla, CA). Carisbamate displays high potency in a broad range of rodent seizure models at doses well below those that produce CNS toxicity. Its mechanism of action has not been elucidated. Acute and chronic nonclinical toxicological studies have not revealed any significant abnormalities other than dose-related CNS toxicity. It is extensively metabolized, chiefly through glucuronidation and oxidation of the aliphatic side chain. There is little evidence of CYP metabolism. It has linear pharmacokinetics. Its clearance is increased by carbamazepine and to a lesser degree by oral contraceptives. Carisbamate slightly increases the clearance of valproic acid and lamotrigine. The most common adverse events in humans are headaches, dizziness, and somnolence, generally mild to moderate, occurring at doses of 1000 mg/day or more. A recently completed phase 2 study for adjunctive use in partial onset seizures showed efficacy at a dose that was well tolerated.