Abstracts

Eslicarbazepine acetate (ESL), formely known as BIA 2-093, is a new CNS-active drug currently in development for the treatment of epilepsy and bipolar disorder. This study aimed to investigate the steady-state pharmacokinetics of ESL once-daily ([italic]qd[/italic]) and twice-daily ([italic]bid[/italic]) regimens in healthy subjects., Single centre, open-label, randomised, crossover study in 12 (6 males and 6 females) healthy volunteers. The study consisted of 8-day treatment periods separated by a washout period of 10-15 days. On each treatment period, the volunteers received either an oral dose of ESL 900 mg [italic]qd [/italic]or ESL 450 mg [italic]bid.[/italic], ESL was extensively and rapidly metabolized to eslicarbazepine (S-licarbazepine, BIA 2-194), the main active metabolite. Plasma levels of the parent drug (ESL) were systematically below the limit of quantification of the assay. Following the last dose of the 8-day ESL 900 mg [italic]qd[/italic] and 450 mg [italic]bid[/italic] regimens, the eslicarbazepine pharmacokinetic parameters are presented in Table 1.[table1]The rate of systemic exposure to eslicarbazepine, as assessed by Cmax, was 33% higher following ESL 900 mg [italic]qd[/italic] in comparison with ESL 450 mg [italic]bid[/italic]. Extent of systemic exposure to eslicarbazepine during a 24-h interval, as assessed by comparing the AUC[tau] of the ESL 900 mg [italic]qd [/italic]regimen (AUC0-24h) with 2 times the AUC[tau] of the ESL 450 mg bid regimen (2 x AUC0-12h), was 3% higher following ESL 900 mg [italic]qd[/italic] in comparison with ESL 450 mg [italic]bid[/italic].
Incidence and characteristics of treatment-emergent adverse events or drug-related adverse events were similar with both treatment alternatives., The extent of exposure to eslicarbazepine during a 24-h interval was similar following ESL 900 mg [italic]qd [/italic]and ESL 450 mg [italic]bid[/italic] regimens, but the rate of exposure was 33% higher following ESL 900 mg [italic]qd[/italic] in comparison with ESL 450 mg [italic]bid. [/italic]Tolerability was similar between [italic]qd[/italic] and [italic]bid[/italic] regimens., (Supported by BIAL (Portela [amp] C[ordf] SA).)