title: Acute or chronic use of lacosamide does not alter its distribution between serum and cerebrospinal fluid.
abstract: OBJECTIVE
  The site of action for antiepileptic drugs (AEDs) 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 AEDs did not affect LCM distribution between serum and CSF.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurosurgery, Wayne State University, Detroit, Michigan, U.S.A.
authors.forename: Sharon K
authors.initials: SK
authors.lastname: Michelhaugh
authors.affiliation: Department of Neurology, Wayne State University, Detroit, Michigan, U.S.A.|Comprehensive Epilepsy Program, Detroit Medical Center, Wayne State University, Detroit, Michigan, U.S.A.
authors.forename: Maysaa
authors.initials: M
authors.lastname: Basha
authors.affiliation: Division of Practice Advancement and Clinical Education, University of North Carolina Eshelman School of Pharmacy, Chapel Hill, North Carolina, U.S.A.
authors.forename: Denise H
authors.initials: DH
authors.lastname: Rhoney
authors.affiliation: Department of Neurology, Wayne State University, Detroit, Michigan, U.S.A.|Comprehensive Epilepsy Program, Detroit Medical Center, Wayne State University, Detroit, Michigan, U.S.A.
authors.forename: Aashit K
authors.initials: AK
authors.lastname: Shah
authors.affiliation: Department of Neurosurgery, Wayne State University, Detroit, Michigan, U.S.A.|Comprehensive Epilepsy Program, Detroit Medical Center, Wayne State University, Detroit, Michigan, U.S.A.|Department of Oncology, Wayne State University, Detroit, Michigan, U.S.A.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Mittal
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000097:blood* / Q000134:cerebrospinal fluid*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000008:administration & dosage / Q000097:blood* / Q000134:cerebrospinal fluid*; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001932:Brain Neoplasms / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy; D003399:Craniotomy / Q000639:trends; D004334:Drug Administration Schedule; D004827:Epilepsy / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy; D005260:Female; D006801:Humans; D000078334:Lacosamide; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000081:Acetamides; D000927:Anticonvulsants; D000078334:Lacosamide
keywords: Antiepileptic drugs; Biodistribution; Blood-brain barrier; Brain tumor-related epilepsy; Pharmacokinetics