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Lack of effect of lacosamide on the pharmacokinetic and pharmacodynamic profiles of warfarin
Author(s) -
Stockis Armel,
Lier Jan Jaap,
Cawello Willi,
Kumke Thomas,
Eckhardt Klaus
Publication year - 2013
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.12192
Subject(s) - lacosamide , warfarin , pharmacodynamics , pharmacokinetics , medicine , crossover study , pharmacology , prothrombin time , anticoagulant , area under the curve , anesthesia , atrial fibrillation , epilepsy , placebo , alternative medicine , pathology , psychiatry
Summary Purpose 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 ( C max ) for S ‐ and R ‐warfarin. Pharmacodynamic end points were area under the international normalized ratio ( INR )–time curve ( AUC INR ), maximum INR ( INR max ), maximum prothrombin time ( PT max ) and area under the PT ‐time curve ( AUC PT ). Key Findings Following warfarin and lacosamide coadministration, C max 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 AUC INR ratio was 1.04 (1.01–1.06). All participants completed the study. Significance 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.