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. Lacosamide (LCM) is an FDA-approved AED for treatment of partial epilepsy with linear pharmacokinetic properties in serum. Its penetration across the blood-brain barrier (BBB) in patients with and without tumor 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. All patients received a single IV LCM dose (200mg over 15min, except for 1 that was 100mg) that 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 and Pearson correlations with GraphPad Prism v.6.04.Results: Data from 30 patients were analyzed, 9 with epilepsy without lesion; (Group1) and 21 with brain tumors (Group2). Data are reported as mean±SD (Table 1). There was a statistical difference between the groups for subject age (Group1 mean=33±14y; Group 2 mean=51±17y; p=0.0139). Serum concentrations were Group1=7.8±2.8µg/mL and Group2=7.6±3.4µg/mL (p>0.05). CSF concentrations were Group1=6.1±2.2µg/mL and Group2=4.7±3.7µg/mL (p>0.05). The CSF/serum ratio for the non-lesional Group1 was 0.80±0.14, while it was much lower for patients with tumors in Group2 at 0.57±0.26. Our findings in the non-lesional group are congruent with a recently reported study by May, et. al., 2015, PMID: 25988882. T-test revealed a significant difference between the LCM CSF/serum ratio for Group1 and Group2 (p=0.022). There was no correlation between subject age and the CSF/serum ratio for either group (Group1 Pearson r=-0.3707, p>0.05; Group2 Pearson r=-0.2174, p>0.05).Conclusions: In this preliminary study, there was a significant difference found between the LCM CSF/serum ratios of patients with brain tumors compared to those without lesions. There was also a difference between the average ages of subjects in each group, consistent with the established demographics of patients undergoing surgical treatment of chronic epilepsy vs. brain tumor patients. Differences between these two patient populations may be related to differential integrity of the BBB, or to tumor-specific expression of an unknown LCM binding protein.