Acute or chronic use of lacosamide does not alter its distribution between serum and cerebrospinal fluid

Summary Objective The site of action for antiepileptic drugs ( AED s) is within the brain; however, cerebrospinal fluid ( CSF ) concentration is highly variable. Lacosamide ( LCM ) is approved by the U.S. Food and Drug Administration ( FDA ) for treatment of partial‐onset seizures in adults, and has linear pharmacokinetics in serum. Penetration across the blood–brain barrier ( BBB ) is unknown. This study aims to provide additional insights into the pharmacokinetics of LCM . Methods Thirty adults undergoing craniotomy for treatment of intractable epilepsy or brain tumor were recruited and were either taking LCM long term (group 1, n = 15), or were LCM naive, receiving LCM as prophylaxis for surgery (group 2, n = 15). All patients received one intravenous ( IV ) dose (15 min infusion) immediately prior to craniotomy. CSF and arterial blood were collected simultaneously following craniotomy. LCM concentrations were measured in serum and CSF . Results LCM concentration differences between groups 1 and 2 for both CSF and serum were statistically significant (p ≤ 0.0005), but there was no statistically significant difference in CSF /serum ratios (group 1 = 0.726 ± 0.231; group 2 = 0.556 ±0.241; p = 0.0585). LCM concentration in serum correlated positively with CSF concentration in group 1 (Pearson r = 0.8527, p < 0.0001). The time interval between the end of dose delivery and sample collection correlated positively with the CSF /serum ratio for the drug‐naive group (Pearson r = 0.6525; p = 0.0084). Treatment with other AED s did not affect LCM distribution between serum and CSF . Significance Although chronic dosing resulted in higher LCM concentrations in serum and CSF compared to drug‐naive patients, the CSF /serum ratio was not affected by LCM pretreatment. These data suggest that LCM serum concentration may reliably predict CSF concentration.