title: No pharmacokinetic interaction between lacosamide and valproic acid in healthy volunteers.
abstract: 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(τ,ss)) 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 AUC(τ,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.
authors.affiliation: UCB Pharma, Global Biostatistics, Alfred-Nobel-Strasse 10, D-40789 Monheim, Germany. willi.cawello@ucb.com
authors.forename: Willi
authors.initials: W
authors.lastname: Cawello
authors.forename: Rainer
authors.initials: R
authors.lastname: Bonn
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004347:Drug Interactions; D006801:Humans; D000078334:Lacosamide; D008297:Male; D014635:Valproic Acid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000081:Acetamides; D000927:Anticonvulsants; D000078334:Lacosamide; D014635:Valproic Acid