title: Comparison of lacosamide concentrations in cerebrospinal fluid and serum in patients with epilepsy.
abstract: OBJECTIVE
  This study was carried out to estimate the exposure of the central nervous system (CNS) to the antiepileptic drug (AED) lacosamide, under steady state conditions, in patients with epilepsy who take oral lacosamide alongside up to three other AEDs.
  
  
  METHODS
  Twenty-seven serum and cerebral spinal fluid (CSF) samples were collected from 21 patients receiving lacosamide for the treatment of epilepsy (50-600 mg/day over two or three doses). This included 23 time-matched pairs of serum and CSF samples from 19 patients. The concentration of lacosamide in each sample was determined using high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Linear regression was used to characterize the relationship between the CSF-to-serum ratio of lacosamide concentration and the time since dosing, the daily lacosamide dose, or the daily dose normalized by volume of distribution (Vd , approximated to total body water), and between the drug concentrations in each compartment (CSF vs. serum).
  
  
  RESULTS
  Concentrations of lacosamide in CSF (mean ± standard deviation [SD] 7.37 ± 3.73 μg/ml, range 1.24-14.95, n = 27) and serum (mean ± SD 8.16 ± 3.82 μg/ml, range 2.29-15.45, n = 27) samples showed a good correlation over the dose range investigated. The mean CSF-to-serum ratio of lacosamide concentrations was 0.897 ± 0.193 (range 0.492-1.254, n = 23 time-matched pairs) and was independent of lacosamide dose.
  
  
  CONCLUSIONS
  Drug concentrations in the CSF are often used to indicate those in the brain interstitial fluid. In patients with epilepsy who follow a stable oral AED dosing regimen, lacosamide concentration in CSF is approximately 85% of that found in serum, suggesting that serum may be a valuable indicator of lacosamide concentration in the CNS.
authors.affiliation: Society for Epilepsy Research, Bielefeld, Germany.
authors.forename: Theodor W
authors.initials: TW
authors.lastname: May
authors.affiliation: Epilepsy Center Bethel, Bielefeld, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Brandt
authors.affiliation: Society for Epilepsy Research, Bielefeld, Germany.
authors.forename: Renate
authors.initials: R
authors.lastname: Helmer
authors.affiliation: Epilepsy Center Bethel, Bielefeld, Germany.
authors.forename: Christian G
authors.initials: CG
authors.lastname: Bien
authors.affiliation: UCB Pharma, Monheim am Rhein, Germany.
authors.forename: Willi
authors.initials: W
authors.lastname: Cawello
mesh_terms: D000081:Acetamides / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; 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; Brain; Epilepsy; Pharmacokinetics