Abstracts

Rationale: The site of therapeutic action for antiepileptic drugs (AEDs) is in the brain; however, pharmacokinetic properties of most AEDs are determined by measuring serum concentration, not cerebrospinal fluid (CSF) concentration. CSF distribution of classic AEDs is highly varied and somewhat dependent on the compound's lipophilicity. Lacosamide (LCM) is a new FDA-approved AED for treatment of partial epilepsy with linear pharmacokinetic properties in serum. Its penetration across the blood-brain barrier (BBB) is unknown. Methods: This study was approved by the Wayne State University Institutional Review Board. Written informed consent was obtained from all patients. Adults undergoing craniotomy for treatment of intractable epilepsy or brain tumor resection were recruited and were either LCM-naïve, receiving LCM as prophylaxis, or taking LCM as part of their ongoing treatment. For all patients, a single IV LCM dose (200 mg over 15 min, except for 1 that was 100 mg) was administered immediately prior to craniotomy. Pooled CSF was collected non-invasively from the sylvian or interhemispheric fissure during surgery. Simultaneously, arterial blood was collected. LCM concentrations were measured by liquid chromatography-tandem mass spectrometry (NMS Labs, Willow Grove, PA). Data were analyzed by unpaired, two-tailed t-test or one-way ANOVA with Tukey's test of multiple comparisons with GraphPad Prism v.6.04. Results: Data from 28 patients were analyzed, 14 using LCM as part of ongoing treatment (Group 1) and 14 LCM-naïve (Group 2). Data are reported as mean ± SD (Table 1). There was no statistical difference between Group 1 and Group 2 for age or LCM dosage (mean= 47y; LCM dosage= 2.35 ± 0.69 mg/kg for Group 1; 2.77 ± 0.61 mg/kg for Group 2). Time between end of LCM infusion and sample collection varied from 16-140 min. Serum concentration for Group 1=9.66 ± 3.3 µg/mL and for Group 2= 5.84 ± 1.8 µg/mL. CSF concentration for Group1 was 7.21 ± 3.6 µg/mL and for Group 2 was 3.05 ± 1.6 µg/mL. Differences between serum and CSF concentrations for Group 1 and Group 2 were significant (p<0.005). The CSF/serum ratio for Group 1= 0.72 ± 0.24 and for Group 2=0.54 ± 0.24. T-test revealed a significant difference between Group 1 and Group 2 (