Lacosamide Levels in Adult Epilepsy Patients Are Influenced by Race (P2.055)

RATIONALE: The antiepileptic Lacosamide (LCM) has 100[percnt] bioavailability, linear pharmacokinetics and little in way of drug interactions. Role of race on LCM serum levels remains unexplored. METHODS: Retrospective chart review of epilepsy clinic patients over two years. LCM serum level was modeled using General Estimating Equation with race, gender, age, LCM daily dose (mg/kg), and concomitant CYP-450 inducing or inhibiting AED’s as independent variables. Besides main-effects, a race-by-daily dose interaction term to assess the differential effect of race on the relationship between the daily dose and LCM levels, and an inducer-by-daily dose interaction term were included. RESULTS: 126 serum samples evaluated from 73 women and 53 men (mean age 41.3) were self identified as African American (AA, n=74) , Caucasian (C, n=45) and 7 others (n=7). Median daily dose of LCM was 345 (range:25-1000) and mean serum concentrations were 6.94 (range: 0-18). Serum LCM levels correlated with the daily LCM dose (R2= 0.16, p< 0.0004) for all groups, without any significant effect of age or gender on LCM levels. African American patients had an overall lower serum levels of LCM (p= 0.017) and demonstrated a significantly weaker correlation between LCM daily dose and serum levels (R2=0.042) as compared to other races (R2=0.47, 0.78 for C and others, respectively, with p= 0.004 and 0.017, comparing AA to C and other, respectively). Although the use of enzyme inducing medications correlated with a lower LCM serum levels (p=0.007), concomitant use of enzyme inducers did not alter the relationship between serum LCM levels and daily dose (p-value = 0.688). CONCLUSIONS: African-Americans showed a weaker correlation between daily-dose and serum LCM levels as compared to non African-Americans, possibly due to faster metabolism, higher excretion or lower absorption of LCM. Future studies to corroborate our findings, and further elucidate possible mechanisms are warranted. Disclosure: Dr. Mahulikar has nothing to disclose. Dr. Shah has received personal compensation from UCB Pharma. Dr. Seraji-Bozorgzad has nothing to disclose. Dr. Basha has nothing to disclose.