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No Pharmacokinetic Interaction Between Lacosamide and Valproic Acid in Healthy Volunteers
Author(s) -
Cawello Willi,
Bonn Rainer
Publication year - 2012
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270011426875
Subject(s) - lacosamide , valproic acid , pharmacokinetics , pharmacology , anticonvulsant , medicine , randomization , chemistry , randomized controlled trial , epilepsy , psychiatry
Two open‐label, randomized, multiple‐dose clinical studies evaluated the potential for pharmacokinetic interaction between the antiepileptic drugs lacosamide and valproic acid. The influence of lacosamide on valproic acid pharmacokinetics (trial A) and valproic acid on lacosamide pharmacokinetics (trial B) was investigated in 32 healthy male volunteers, 16 in each trial. Volunteers in trial A received valproic acid (300 mg bid) with randomization to either early or late addition of lacosamide (200 mg bid). Those in trial B received lacosamide (200 mg bid) with randomization to either early or late addition of valproic acid (300 mg bid). Area under the concentration‐time curve during a 12‐hour dosing interval at steady state (AUC TSS ) and maximum steady‐state plasma drug concentration (C max, ss ) were measured for each drug alone and together and tested for equivalence. The point estimates (90% confidence intervals) for AUCt, ss and C max, ss were 104% (99%–109%) and 101% (97%–107%), respectively, for valproic acid and 100% (98%–103%) and 101% (96%–107%), respectively, for lacosamide, which were within the generally accepted equivalence range of 80% to 125%. No changes in the rate or extent of absorption, terminal half‐life, or time to maximum concentration were observed. These results suggest that lacosamide and valproic acid have no relevant pharmacokinetic drug‐drug interaction.