Intravenous brivaracetam in status epilepticus: Correlation between loading dose, plasma levels and clinical response

Abstract

Brivaracetam is available in intravenous formulation, and its favourable pharmacokinetic profile makes it a promising agent in the treatment of status epilepticus (SE). Its availability as an intravenous formulation and its favourable pharmacokinetic profile make it a promising agent in the treatment of status epilepticus. Our aim was to assess the correlation between BRV exposure and clinical response.We retrospectively studied all consecutive SE patients treated with BRV in our centre from September 2016 to March 2018. Correlations between loading doses, plasma concentrations, extrapolated exposures (approach based on a population pharmacokinetics model) and the clinical response (defined as BRV being able to resolve SE without the need of further treatment), were analysed.Among 14 patients, 7 (50%) responded to BRV. Responders received significantly greater median loading dosage per body weight (3.3 mg/kg) compared to non-responders (1.5 mg/kg) (p = 0.02); no responders had loading doses below 1.9 mg/kg. There was a significant correlation of the clinical response with calculated exposure parameters, whereas measured BRV concentrations did not.BRV doses higher than 1.9 mg/kg are associated with greater probabilities of response in SE; consequently, a minimum dose of 2 mg/kg seems advisable in treatment of SE. It is unclear whether increasing further BRV loading doses would provide any additional benefit. BRV concentrations performed outside the frame of a standardised protocol merely ascertain BRV administration. This study is however limited by its small sample size.