Abstracts

Rationale: Because the pharmacokinetics and the pharmacodynamics of antiepileptic drugs may be altered by advancing age, an understanding of the clinical pharmacology of these agents in elderly subjects is essential for rational prescribing (Perucca et al., 2006, Epi Res 68S:S49-S63). Brivaracetam is a novel high-affinity synaptic vesicle protein 2A (SV2A) ligand and also displays inhibitory activity at neuronal voltage-dependent sodium channels. The efficacy and safety of brivaracetam are currently being investigated in Phase III clinical trials in patients with epilepsy, in the dose range between 5 and 150 mg/day. The purpose of the study was to assess the pharmacokinetics, safety and tolerability of brivaracetam in healthy elderly subjects. Methods: Sixteen healthy male and female subjects (ten aged 65-75, and six aged >75 years) were evaluated after one single 200 mg oral dose and during a 10-day course of 200 mg b.i.d. oral administration of brivaracetam. Pharmacokinetic parameters were calculated from plasma and urine concentration versus time profiles. Safety and tolerability were assessed by recording of adverse events, laboratory tests and neurological examinations. Results: In healthy male and female elderly subjects, brivaracetam was rapidly absorbed following both single and repeated oral administration with median time to peak plasma concentration at 1.5 hours. Plasma concentrations decayed mono-exponentially, with a median half-life of 7.7 hours (range 6.5-9.8) and 8.6 hours (range 7.8-11.4) in the 65-75 and >75 years groups, respectively. Steady state plasma clearance (geometric mean) of brivaracetam in elderly males was slightly lower (0.74 mL/min/kg) than in young healthy males (0.83 mL/min/kg). Brivaracetam was generally well tolerated. Adverse events were of mild intensity, transient (mainly occurring on the first day), similar across age subgroups and comparable to those observed in a younger population. No clinically relevant abnormalities were observed in laboratory parameters, vital signs or neurological examinations. Conclusions: In healthy elderly subjects, the pharmacokinetics and tolerability of brivaracetam were comparable to those observed in a younger population, indicating that no dose adjustment of brivaracetam in elderly patients would be required. Study sponsored by UCB.