Abstracts

Rationale: Clobazam (Onfi brand name in the US) is increasingly used in patients with epilepsy (PWE) beyond its approval in the U.S. for LGS. A few studies of pharmacokinetics (PK) of the drug have been reported in children, patients primarily with LGS and in single dose studies. We sought to examine convenience PK statistics in an adult population of PWE and if any impact of switch to generic exists on these PK statistics.  Methods: This was a retrospective cohort study of adults with epilepsy attending a Level 4 Epilepsy Center clinic at a single academic medical center. Most subject were instructed to check morning trough levels and took the medicine in every 12 hours. Labs were drawn typically in steady state conditions and processed by Labcorp and NMS Laboratories. Charts were reviewed for lab data, demographics and other clinical data.  Results: 45 subjects had sufficient data to allow examining relationships of concentration with other clinical variables. Mean age was 36 yrs (range 20 to 70 yrs) at last utilized blood level, 51% were male, and mean age of epilepsy-onset was 12 yrs old (range 2 mos to 55 yrs old). 31% of patients had concentrations assessed when on generic clobazam. Clobazam concentration cohort summary statistics were in ng/mL: mean 263 (sd 189), median 211 (IQR 152-326), and range 21-847.Concentration/dose was mean 10.1 (sd 6.1), median 8.5 (IQR 5.7-14.9), and range 1.8-22.6.Desmethylclobazam concentration cohort summary statistics were in ng/mL: mean 2330 (sd 1810), median 1688 (IQR 998-3302), and range 266-7507.Concentration/dose was mean 89.7 (sd 59.9), median 69.1 (IQR 39.3-124.5), and range 18.8-250.2. Regression analysis showed that dose (coefficient 6.3, p<0.001) and using an enzyme inducing AED (coefficient -170, p<0.001) were associated with clobazam concentrations. Age, enzyme-inhibiting AED use, and taking a generic were not associated with changes in concentration. A similar analysis was performed for desmethylclobazam, and dose was the only variable found to associate with concentration.  Conclusions: This small retrospective 'real life' PK study demonstrated that using a higher bound of the published reference range for clobazam (30-300) and desmethylclobazam (300-3000) for clinical use is feasible. Enzyme-inducing AED was associated with LOWER clobazam concentrations. Generic clobazam usage DID NOT impact serum concentrations. Further analyses in better-controlled studies (e.g. serum timing and drug interactions) on PK values and dose, concentration, and clinical responses should be considered.  Funding: No funding