Abstracts

Rationale: Lacosamide (LCM) is an antiepileptic medication approved for adjuvant treatment of partial onset seizures in adults. It has a favorable profile with 100% bioavailability,linear pharmacokinetics and a steady state that is reached within 3 days. In this study, we investigate the effects of dose, age, gender, race and concomitant AEDs on the LCM serum levels in patients with epilepsy.Methods: In a retrospective review, LCM levels serum levels of 91 patients seen in the epilepsy clinic between Jan. 2013 through Dec. 2014 were evaluated. Patient demographics (race, gender, and age), LCM daily dose (mg/kg) and LCM levels concomitant antiepileptic drugs (AED) (classified into CYP-450 inducers and inhibitors) were collected. Statistical analysis was performed using STATA software. We used the method of General Estimating Equation (GEE) with the identity transformation, normal distribution and exchangeable correlation function, to avoid inflation of results due to multiple samples from the same patient. Model consisted of main-effect terms and race-by-daily dose interaction term to assess the differential effect of race on the relationship between the daily dose and LCM levels. The same approach was also used to explore the effect of concomitant use of CYP-450 inducers. Descriptive data of continuous variables are expressed as mean ± standard deviation. Modal data is expressed as median ± range. P-value < 0.05 was considered significant.Results: As summarized in table 1, we collected 126 serum samples from 91 patients: M/F ratio 39/52, age 41 ± 13, who identified themselves as African-American (AA, n=74), Caucasian (C, n=45) or other (n=7). Overall, serum LCM levels (mean 6.94 ± 3.8) correlated with the daily LCM dose (mean 4.3± 2.3, R2=­­ 0.16, p< 0.0004). Age and gender did not affect the LCM levels significantly. The effect of race on serum LCM values revealed 1) a direct effect, i.e. suggesting that AA patients had an overall lower serum levels of LCM (p= 0.017) and 2) an interaction of race by daily-dose effect, suggesting that AA patients demonstrated a weaker relationship between LCM daily dose and serum levels with a slope of 0.36±0.17, 1.5 ± 0.24 and 1.9 ± 0.41and an R2 of 0.042, 0.47, 0.78 for AA, C and others, respectively (p= 0.004 and 0.017 comparing AA to C and other, respectively, Figure 1.) Use of enzyme inducing medications correlated with lower LCM serum levels (p=0.007), however, there was not a significant effect of enzyme inducers on the relationship between serum LCM levels and daily dose (p-value = 0.688).Conclusions: Serum LCM concentrations were age independent and race dependent with AA achieving significantly lower serum levels compared to C patients at similar LCM dosing. This could represent a genetic cause of faster metabolism or excretion, or decreased absorption of the drug in AA population. The lower LCM levels are likely due to the presence of lower daily dosing of LCM and likely not related to drug-drug interaction, as previously reported. Monitoring AED levels continues to be useful in new AEDs and in identifying the therapeutic range unique to the patient.