EFFECT OF ESLICARBAZEPINE ACETATE ON THE STEADY-STATE PHARMACOKINETICS OF DIGOXIN IN HEALTHY SUBJECTS
Abstract number :
2.261
Submission category :
Year :
2005
Submission ID :
5567
Source :
www.aesnet.org
Presentation date :
12/3/2005 12:00:00 AM
Published date :
Dec 2, 2005, 06:00 AM
Authors :
Joana Maia, Luis Almeida, Manuel Vaz-da-Silva, Eva Soares, Susana Tavares, Amilcar Falcao, and Patricio Soares-da-Silva
To investigate the effect of eslicarbazepine acetate, a new voltage-gated sodium channel blocker, on the steady-state pharmacokinetics of digoxin. ingle-centre, randomized, double-blind, placebo-controlled, two-way crossover study in 12 healthy subjects. The study consisted of two 8-day treatment periods separated by a washout of 10 or more days. On each period, subjects received either a daily oral dose of eslicarbazepine acetate (ESL) 1200 mg once-daily or placebo (PLA) concomitantly with a digoxin once-daily dose of 0.5 mg/day on Days 1 and 2 and 0.25 mg/day on Days 3 to 8. Minimum serum digoxin concentration (C[sub]min[/sub]) at Days 6, 7 and 8 was respectively 445, 452 and 633 pg/mL with PLA and 475, 522 and 561 pg/mL with ESL. Serum digoxin concentration-time profile post last digoxin dose (Day 8) in each period is presented in Figure 1. Mean ([plusmn]SD) maximum serum digoxin concentration (C[sub]max[/sub]) and area under the concentration-time curve over the dosing interval (AUC[sub][tau][/sub]) following administration of digoxin with PLA were 2350 (1034) pg/mL and 17607 (5599) pg.h/mL, respectively. Following administration with ESL, mean ([plusmn]SD) C[sub]max[/sub]) and AUC[sub][tau][/sub] were 1909 (596) pg/mL and 16595 (3801) pg.h/mL, respectively. Digoxin C[sub]max[/sub] occurred (t[sub]max[/sub]) at 1 h post-dose in both periods. Point estimate (PE) and corresponding 90% confidence intervals (90%CI) of the PLA/ESL C[sub]max[/sub] geometric mean ratio were 0.85 and 0.68-1.07. The PLA/ESL digoxin AUC[sub][tau][/sub] geometric mean ratio presented a PE of 0.96 and a 90%CI of 0.90-1.03. The 15% decrease in digoxin C[sub]max[/sub], when digoxin was administered concomitantly with ESL, is not expected to affect digoxin efficacy because the extent of exposure (as assessed by AUC[sub][tau][/sub]) was similar and C[sub]max[/sub] decrease may reduce the probability of adverse events related with digoxin peak exposure. Eslicarbazepine acetate, at the dose of 1200 mg once-daily, has no relevant effect on the steady-state extent of systemic exposure to digoxin.[figure1]
