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Effect of eslicarbazepine acetate on the pharmacokinetics of digoxin in healthy subjects
Author(s) -
Vaz da Silva Manuel,
Costa Raquel,
Soares Eva,
Maia Joana,
Falcão Amílcar,
Almeida Luis,
Soares da Silva Patrício
Publication year - 2009
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.2009.00691.x
Subject(s) - digoxin , bioequivalence , pharmacokinetics , crossover study , placebo , medicine , confidence interval , dosing , sodium channel blocker , geometric mean , pharmacology , anesthesia , sodium , heart failure , sodium channel , chemistry , mathematics , alternative medicine , pathology , statistics , organic chemistry
Eslicarbazepine acetate (ESL) is a new‐generation voltage‐gated sodium channel blocker, which has been demonstrated to be effective and well tolerated in the treatment of epilepsy. The primary objective of this study was to investigate the effect of ESL on the pharmacokinetics of digoxin. This study was a randomized, double‐blind, placebo‐controlled, two‐way crossover study of 12 healthy subjects (six men and six women). The study included two 8‐day treatment periods with a washout of ≥10 days. In each period, subjects received either ESL 1200 mg once‐daily or placebo, concomitantly with a loading oral dose of digoxin 0.5 mg on days 1 and 2, followed by a once‐daily maintenance dose of 0.25 mg on days 3–8. Maximum serum digoxin plasma concentrations ( C max ) were reached ( t max ) at 0.5–2.0 h post‐dose (median = 1.0 h) and at 0.5–4.0 h post‐dose (median = 1.0 h) with Reference (digoxin plus placebo) and Test (digoxin plus ESL) treatments, respectively. The Test/Reference digoxin geometric mean ratios and 90% confidence intervals (90% CI) were 0.96 and 0.90–1.03 for the area under the plasma concentration–time curve over the dosing interval (AUC 0–24 ) and 0.85 and 0.68–1.07 for C max . The 90% CI was within the bioequivalence range (0.80–1.25) for AUC 0–24 , thus demonstrating bioequivalence. The 90% CI was outside the 0.80–1.25 range for digoxin C max , but it appeared to be caused by a higher variability in digoxin C max following co‐administration of digoxin with placebo than with ESL. Co‐administration of ESL and digoxin was well tolerated. Concomitant administration of ESL has no clinically relevant effect in the systemic exposure to digoxin.