Effect of eslicarbazepine acetate on the pharmacokinetics of digoxin in healthy subjects.
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 >or=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.
Vaz da Silva
Manuel
M
Department of Research and Development, BIAL - Portela & Co, SA, S Mamede do Coronado, Portugal.
Costa
Raquel
R
Soares
Eva
E
Maia
Joana
J
Falcão
Amílcar
A
Almeida
Luis
L
Soares da Silva
Patrício
P
D000284:Administration, Oral; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects / Q000494:pharmacology*; D019540:Area Under Curve; D002316:Cardiotonic Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D003984:Dibenzazepines / Q000009:adverse effects / Q000494:pharmacology*; D004077:Digoxin / Q000009:adverse effects / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D013810:Therapeutic Equivalency; D055815:Young Adult
D000927:Anticonvulsants; D002316:Cardiotonic Agents; D003984:Dibenzazepines; D004077:Digoxin; C416835:eslicarbazepine acetate