title: Pharmacokinetics of lacosamide and omeprazole coadministration in healthy volunteers: results from a phase I, randomized, crossover trial.
abstract: BACKGROUND
  The antiepileptic drug lacosamide has a low potential for drug-drug interactions, but is a substrate and moderate inhibitor of the cytochrome P450 (CYP) enzyme CYP2C19.
  
  
  OBJECTIVE
  This phase I, randomized, open-label, two-way crossover trial evaluated the pharmacokinetic effects of lacosamide and omeprazole coadministration.
  
  
  METHODS
  Healthy, White, male volunteers (n = 36) who were not poor metabolizers of CYP2C19 were randomized to treatment A (single-dose 40 mg omeprazole on days 1 and 8 together with 6 days of multiple-dose lacosamide [200-600 mg/day] on days 3-8) and treatment B (single doses of 300 mg lacosamide on days 1 and 8 with 7 days of 40 mg/day omeprazole on days 3-9) in pseudorandom order, separated by a ≥ 7-day washout period. Area under the concentration-time curve (AUC) and peak concentration (C(max)) were the primary pharmacokinetic parameters measured for lacosamide or omeprazole administered alone (reference) or in combination (test). Bioequivalence was determined if the 90 % confidence interval (CI) of the ratio (test/reference) fell within the acceptance range of 0.8-1.25.
  
  
  RESULTS
  The point estimates (90 % CI) of the ratio of omeprazole + lacosamide coadministered versus omeprazole alone for AUC (1.098 [0.996-1.209]) and C(max) (1.105 [0.979-1.247]) fell within the acceptance range for bioequivalence. The point estimates (90 % CI) of the ratio of lacosamide + omeprazole coadministration versus lacosamide alone also fell within the acceptance range for bioequivalence (AUC 1.133 [1.102-1.165]); C(max) 0.996 (0.947-1.047).
  
  
  CONCLUSIONS
  Steady-state lacosamide did not influence omeprazole single-dose pharmacokinetics, and multiple-dose omeprazole did not influence lacosamide single-dose pharmacokinetics.
authors.affiliation: UCB Biosciences GmbH, UCB Pharma, Global Statistical Sciences, Alfred-Nobel-Str. 10, 40789, Monheim am Rhein, Germany, Willi.Cawello@ucb.com.
authors.forename: Willi
authors.initials: W
authors.lastname: Cawello
authors.forename: Christa
authors.initials: C
authors.lastname: Mueller-Voessing
authors.forename: Andreas
authors.initials: A
authors.lastname: Fichtner
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D018592:Cross-Over Studies; D004361:Drug Tolerance; D064420:Drug-Related Side Effects and Adverse Reactions; D064368:Healthy Volunteers; D006801:Humans; D000078334:Lacosamide; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D000081:Acetamides; D000078334:Lacosamide; D009853:Omeprazole