title: Lacosamide serum concentrations in adult patients with epilepsy: the influence of gender, age, dose, and concomitant antiepileptic drugs.
abstract: OBJECTIVE
  Lacosamide (LCM), a new antiepileptic drug (AED) approved as adjunctive therapy for the treatment of patients with partial-onset seizures, has limited pharmacokinetic and drug interaction data. The main objectives of the present study were to investigate the effects of dose, age, gender, and hepatic enzyme-inducing AEDs on the pharmacokinetics of LCM as assessed by steady state serum LCM values.
  
  
  METHODS
  An LCM AED therapeutic drug monitoring database was analyzed with regard to LCM serum concentrations and other relevant patient and AED drug information. One hundred twenty eight sera were identified. These were collected from 68 women and 61 men aged 19-66 years, who were prescribed a median LCM dose of 300 mg (range 50-600 mg).
  
  
  RESULTS
  Serum LCM concentrations were observed in the following main groupings: LCM monotherapy (n = 5), LCM with nonenzyme-inducing AEDs (n = 50), LCM with enzyme-inducing AEDs (n = 49), LCM with valproic acid (n = 20), and LCM with enzyme-inducing AEDs plus valproic acid (n = 4). Analysis of variance showed a correlation of dose with LCM concentrations (r = 0.53, P < 0.001), and women had statistically higher mean LCM concentration than did men, 37.2 ± 23.6 versus 26.8 ± 12.9 μmol/L (P = 0.001). Serum LCM concentrations were significantly lower (P = 0.002) in the enzyme-inducing AED group (carbamazepine and phenytoin) compared with the LCM monotherapy group and the nonenzyme-inducing group, 23.5 ± 11.0, 34.5 ± 7.7, and 32.7 ± 17.9 μmol/L, respectively.
  
  
  CONCLUSIONS
  Serum LCM concentrations increased dose dependently, were age independent, and were higher in women compared with men. Carbamazepine and phenytoin can significantly decrease serum LCM concentrations, probably via induction of LCM metabolism.
authors.affiliation: *Epilepsy Society, Chalfont Centre for Epilepsy, Chalfont St Peter; †Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology; and ‡National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
authors.forename: Sofia
authors.initials: S
authors.lastname: Markoula
authors.forename: Rute
authors.initials: R
authors.lastname: Teotonio
authors.forename: Neville
authors.initials: N
authors.lastname: Ratnaraj
authors.forename: John S
authors.initials: JS
authors.lastname: Duncan
authors.forename: Josemir W
authors.initials: JW
authors.lastname: Sander
authors.forename: Philip N
authors.initials: PN
authors.lastname: Patsalos
mesh_terms: D000081:Acetamides / Q000097:blood* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000097:blood* / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002220:Carbamazepine / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D016903:Drug Monitoring / Q000379:methods; D004359:Drug Therapy, Combination / Q000379:methods; D004790:Enzyme Induction / Q000187:drug effects; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000078334:Lacosamide; D008297:Male; D008875:Middle Aged; D010672:Phenytoin / Q000627:therapeutic use; D012189:Retrospective Studies; D012640:Seizures / Q000188:drug therapy; D014635:Valproic Acid / Q000627:therapeutic use
chemical_list: D000081:Acetamides; D000927:Anticonvulsants; D002220:Carbamazepine; D000078334:Lacosamide; D014635:Valproic Acid; D010672:Phenytoin