Does Xcopri (cenobamate) have measurable serum drug levels?

Cenobamate (Xcopri) Serum Drug Level Monitoring

Yes, cenobamate (Xcopri) does have measurable serum drug levels that can be quantified using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS).

Pharmacokinetic Properties of Cenobamate

• Cenobamate has a long elimination half-life of approximately 50-60 hours, allowing for steady-state plasma concentrations to be attained after approximately two weeks of once daily dosing 1
• At least 88% of cenobamate is absorbed following oral administration, with median time to maximum concentration (Tmax) ranging from 1 to 4 hours 1
• Cenobamate is extensively metabolized, primarily through glucuronidation via UGT2B7 and to a lesser extent by UGT2B4, and by oxidation via multiple CYP enzymes (CYP2E1, CYP2A6, CYP2B6, and to a lesser extent by CYP2C19 and CYP3A4/5) 1
• Following administration of radiolabeled cenobamate, unchanged cenobamate accounted for greater than 98% of the total AUC of radioactivity in plasma, making it the primary circulating component 2

Analytical Methods for Measuring Cenobamate

• Cenobamate serum levels can be accurately quantified using UHPLC-MS/MS methodology, which has been validated according to current guidelines 3
• This analytical approach allows for therapeutic drug monitoring in patients receiving cenobamate therapy, particularly useful in cases of suspected non-adherence, treatment failure, or drug interactions 3

Clinical Applications of Cenobamate Level Monitoring

• Monitoring cenobamate plasma concentrations may be particularly valuable when:
  • Assessing medication adherence in patients with inadequate seizure control 3
  • Managing complex drug interactions with concomitant antiseizure medications 4
  • Evaluating potential toxicity or adverse effects 5
  • Optimizing dosing in patients with renal or hepatic impairment 1

Drug Interactions and Level Monitoring Considerations

• Cenobamate can significantly affect the plasma concentrations of other co-administered antiseizure medications (ASMs), including:
  • Increasing levels of phenytoin, phenobarbital, and the active metabolite of clobazam 4
  • Decreasing levels of carbamazepine and lamotrigine 4
• Conversely, some ASMs can affect cenobamate levels:
  • Plasma cenobamate multiple-dose exposure (Cmax, AUC) decreased with co-administration of phenytoin by 27-28% 1
• These bidirectional interactions highlight the potential value of therapeutic drug monitoring in patients on polytherapy 4

Clinical Correlation with Serum Levels

• Preliminary clinical data has shown a linear increase in plasma cenobamate concentrations corresponding with dose increases, suggesting a predictable dose-concentration relationship 3
• In a small study of non-adult patients, seizure freedom was achieved at cenobamate doses of 150 mg per day, correlating with specific plasma concentrations 3

Practical Considerations for Monitoring

• Unlike some other antiseizure medications, there are currently no established therapeutic range guidelines for cenobamate serum levels 1, 3
• The timing of blood sample collection should consider cenobamate's pharmacokinetic profile, with peak levels occurring 1-4 hours post-dose 1
• When interpreting cenobamate levels, clinicians should consider factors that may affect pharmacokinetics, including:
  • Renal function (cenobamate plasma AUC increases with renal impairment) 1
  • Concomitant medications that may induce or inhibit metabolizing enzymes 4
  • Patient-specific factors such as age, weight, and compliance 1

Limitations and Caveats

• Therapeutic drug monitoring for cenobamate is still evolving, with limited published data on correlation between serum levels and clinical efficacy or toxicity 3
• Access to cenobamate assays may be limited to specialized laboratories with appropriate UHPLC-MS/MS capabilities 3
• Interpretation of cenobamate levels should always be done in the context of clinical response and tolerability rather than targeting specific concentrations 4