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Interactions
Using cenobamate together with other central nervous system depressants such as barbiturates, benzodiazepines or alcohol may result in increased drowsiness and other central nervous system symptoms.Cenobamate induces the enzymes CYP3A4 and CYP2B6 and can therefore decrease blood concentrations of drugs that are metabolized by these enzymes (for example midazolam and bupropion, respectively). Conversely, it inhibits the enzyme CYP2C19, potentially increasing concentrations of drugs metabolized by this enzyme (for example omeprazole). Pharmacology
Mechanism of action
Cenobamate is a voltage-gated sodium channel (VGSC) blocker. It is a selective blocker of the inactivated state of VGSCs, preferentially inhibiting persistent sodium current. It has been proposed that cenobamate additionally enhances presynaptic release of γ-aminobutyric acid (GABA), thereby increasing inhibitory GABAergic neurotransmission. Pharmacokinetics
Cenobamate is absorbed from the gut to at least 88% and reaches highest concentrations in the blood plasma after one to four hours. When in the bloodstream, 60% of the substance are bound to plasma proteins, mostly to albumin. Cenobamate is inactivated mainly by glucuronidation via the enzyme UGT2B7 and to a lesser extent UGT2B4. The enzymes CYP2E1, CYP2A6, CYP2B6, CYP2C19 and CYP3A4 play smaller roles in the drugs metabolism.Steady state conditions are reached after 14 days. Cenobamate and its metabolites are mostly eliminated via the urine and only to 5.2% via the faeces. The terminal half-life is 50 to 60 hours. History
The safety and efficacy of cenobamate to treat partial-onset seizures was established in two randomized, double-blind, placebo-controlled studies that enrolled 655 adults.