Abstract Details

Cenobamate is an antiseizure medication approved in the US for treatment of focal (partial-onset) seizures in adults. Epilepsy patients should be titrated to a cenobamate dose that provides the best efficacy with acceptable tolerability. Plasma concentrations may be used to aid physicians in evaluating compliance, breakthrough seizures, side effects, etc. 

To determine a reference concentration range for cenobamate by analyzing steady state trough plasma concentrations during the maintenance phase of two adequate and well controlled studies (YKP3089C013 [C013]/YKP3089C017 [C017]) in patients who achieved 50% seizure reduction (50% SR) and seizure freedom (SF; 100% seizure reduction).

Trough cenobamate plasma concentrations were obtained periodically during the maintenance phase of study C013 and C017. Average cenobamate concentrations were associated with each patient who achieved 50% SR and SF at doses of 100 (n=42, n=4, respectively), 200 (n=95, n=32, respectively) or 400 mg/day (n=50, n=18, respectively) during the maintenance phase. Box (including 90% of patients) and whisker (entire range) plots comparing the three cenobamate dose groups were developed. A C_trough range that covered at least 95% of the total population for 50% SR and SF was determined. A toxic range was not established.

The range of concentrations (µg/mL) during the maintenance phase for 90% of patients with 50% SR taking 100 mg/day was 4.6-9.3, taking 200 mg/day was 11.3-18.7, and taking 400 mg/day was 20.8-35.2. The range of concentrations (µg/mL) during the maintenance phase for 90% of patients with SF taking 100 mg/day was 5.1-9.7, taking 200 mg/day was 10.8-19.8, and taking 400 mg/day was 21.9-35.8. Overall, cenobamate trough concentrations for 95% of patients with 50% SR or SF lay between 5 µg/mL and 35 µg/mL.

A suggested trough plasma concentration reference range (not a target therapeutic range) of 5-35 µg/mL covered 95% of patients who achieved 50% SR or 100% SR.