The purpose of the study in this paper was to compare, in healthy volunteers from both genders, the pharmacokinetic profiles of lacosamide, aiming to assess the bioequivalence between two formulations: lacosamide200 mg film-coated tablet, registered by Zodiac Produtos Farmacêuticos S.A. PK analysis indicated low interindividual and intraindividual variability of PK parameters. Įlimination of lacosamide from plasma occurs with a terminal half-life (t½) of 12–14 h in young subjects and 14–16 h in elderly subjects. Approximately 40% of lacosamide is eliminated unchanged via renal excretion mechanisms. Unchanged lacosamide predominates in human plasma after administration, with circulating metabolites having no known pharmacological activity. It is primarily metabolized via CYP2C19 (demethylation) to an inactive O-desmethyl metabolite (30%). Plasma protein binding for lacosamide is low (approximately< 15 %) in healthy subjects as well as in patients with partial-onset seizures. A dose-proportional increase of Cmax and AUC was observed after a single oral lacosamide dose ranging from 100 to 800 mg. Intake of food does not affect the area under the plasma concentration–time curve (AUC) or Cmax of lacosamide. The absorption is complete with almost 100% bioavailability. įollowing oral administration, plasma concentrations of lacosamide increased rapidly and reached a maximum at about 0.5–4 h post dose (tmax). Lacosamide has been proposed for the treatment of neuropathic pain of various etiologies in patients who do not respond to standard treatments. It enhances the inactivation of voltage-gated sodium channels, leading to the stabilization of hyper-excitable neuronal membranes. It was approved by both the FDA and the EMEA in 2008. Lacosamide is indicated as monotherapy or adjunctive therapy for patients with partial-onset seizures and focal epilepsies. Lacosamide has a molecular weight of 250.3 and is classified under the Biopharmaceutical Classification System as a Class 1 compound (i.e. Lacosamide has amphiphilic properties, on one hand being sufficiently water soluble to support complete and fast absorption after an oral dose, and on the other hand being sufficiently lipophilic to cross the blood–brain barrier. Lacosamide, chemical name (R)-2-acetamido-N-benzyl-3-methoxypropionamide, is a functionalized amino acid. Keywords: lacosamide, film-coated tablets, fasting conditions, bioequivalence, chromatography
Under fasting condition, the test (lacosamide 200 mg film-coated tablets, Monte Verde S.A.) and reference (Vimpat® 200 mg film-coated tablets, Aesica Pharmaceuticals GmbH) formulations were considered bioequivalent since the 90% CIs for the geometric mean test/reference ratios were within ANVISA’s predetermined range of 80% to 125%. Confidence intervals (CI90%) for the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC0-t) were determined by calculating log-transformed data. Blood samples were taken during 72 h and plasmatic concentrations were determined using a validated HPLC-MS/MS method. The study was single dose, randomized, open label, two-period crossover, with Brazilian males and females healthy subjects. Bioavailability from different formulations of lacosamide200 mg film-coated tablets was compared in a bioequivalence study under fasting conditions.
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