title: Lack of effect of lacosamide on the pharmacokinetic and pharmacodynamic profiles of warfarin.
abstract: OBJECTIVE
  The aim of this study was to evaluate the effect of the antiepileptic drug lacosamide on the pharmacokinetics and pharmacodynamics of the anticoagulant warfarin.
  
  
  METHODS
  In this open-label, two-treatment crossover study, 16 healthy adult male volunteers were randomized to receive a single 25-mg dose of warfarin alone in one period and lacosamide 200 mg twice daily on days 1-9 with a single 25 mg dose of warfarin coadministered on day 3 in the other period. There was a 2-week washout between treatments. Pharmacokinetic end points were area under the plasma concentration-time curve (AUC(0,last) and AUC(0,∞) ) and maximum plasma concentration (Cmax ) for S- and R-warfarin. Pharmacodynamic end points were area under the international normalized ratio (INR)-time curve (AUCINR ), maximum INR (INRmax ), maximum prothrombin time (PTmax ) and area under the PT-time curve (AUCPT ).
  
  
  RESULTS
  Following warfarin and lacosamide coadministration, Cmax and AUC of S- and R-warfarin, as well as peak value and AUC of PT and INR, were equivalent to those after warfarin alone. In particular, the AUC(0,∞) ratio (90% confidence interval) for coadministration of warfarin and lacosamide versus warfarin alone was 0.97 (0.94-1.00) for S-warfarin and 1.05 (1.02-1.09) for R-warfarin, and the AUCINR ratio was 1.04 (1.01-1.06). All participants completed the study.
  
  
  CONCLUSIONS
  Coadministration of lacosamide 400 mg/day did not alter the pharmacokinetics of warfarin 25 mg or the anticoagulation level. These results suggest that there is no need for dose adjustment of warfarin when coadministered with lacosamide.
authors.affiliation: UCB Pharma, Braine-l'Alleud, Belgium. armel.stockis@ucb.com
authors.forename: Armel
authors.initials: A
authors.lastname: Stockis
authors.forename: Jan Jaap
authors.initials: JJ
authors.lastname: van Lier
authors.forename: Willi
authors.initials: W
authors.lastname: Cawello
authors.forename: Thomas
authors.initials: T
authors.lastname: Kumke
authors.forename: Klaus
authors.initials: K
authors.lastname: Eckhardt
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000328:Adult; D000925:Anticoagulants / Q000097:blood / Q000493:pharmacokinetics*; D000927:Anticonvulsants / Q000494:pharmacology*; D019540:Area Under Curve; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005500:Follow-Up Studies; D006801:Humans; D019934:International Normalized Ratio; D000078334:Lacosamide; D008297:Male; D013997:Time Factors; D014859:Warfarin / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000081:Acetamides; D000925:Anticoagulants; D000927:Anticonvulsants; D000078334:Lacosamide; D014859:Warfarin
keywords: Antiepileptic drug; Lacosamide; Pharmacodynamics; Pharmacokinetics; Warfarin