title: Pharmacological interactions between brivaracetam and ethanol in healthy males.
abstract: This double-blind, randomized, three-way crossover study explored the potential pharmacokinetic and pharmacodynamic interactions between ethanol and brivaracetam in 18 healthy males, as required for the development of CNS-active drugs. Subjects received (A) ethanol+brivaracetam, (B) ethanol placebo+brivaracetam and (C) ethanol+brivaracetam placebo. Ethanol was infused as a 5.5-hour intravenous clamp with the first 0.5-hour as loading phase to a target level of 0.6 g/L, and brivaracetam was orally administered as a single 200 mg dose. No relevant pharmacokinetic interactions were observed. Co-administration of brivaracetam and ethanol resulted in decreased saccadic peak velocity, smooth pursuit, adaptive tracking and VAS alertness, and increased body sway, saccadic reaction time and VAS score for ethanol effect compared with brivaracetam alone or ethanol alone. Additionally, the immediate word recall scores were generally lower when brivaracetam was co-administered with ethanol, whereas the delayed word test did not show clear additional effects. A post-hoc exploratory analysis for supra-additivity suggested that most pharmacodynamic effects were likely to be additive in nature, except for adaptive tracking, which appeared to be slightly supra-additive. In conclusion, brivaracetam increased ethanol effects on psychomotor function, attention and memory in healthy males. Intake of brivaracetam with alcohol is not recommended.
authors.affiliation: 1 Centre for Human Drug Research, Leiden, the Netherlands.
authors.forename: Annelieke C
authors.initials: AC
authors.lastname: Kruithof
authors.affiliation: 2 UCB Pharma, Braine-l'Alleud, Belgium.
authors.forename: Shikiko
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: 1 Centre for Human Drug Research, Leiden, the Netherlands.
authors.forename: Pierre Am
authors.initials: PA
authors.lastname: Peeters
authors.affiliation: 1 Centre for Human Drug Research, Leiden, the Netherlands.
authors.forename: Marieke L
authors.initials: ML
authors.lastname: de Kam
authors.affiliation: 1 Centre for Human Drug Research, Leiden, the Netherlands.
authors.forename: Rob Gja
authors.initials: RG
authors.lastname: Zuiker
authors.affiliation: 1 Centre for Human Drug Research, Leiden, the Netherlands.
authors.forename: Jasper
authors.initials: J
authors.lastname: Stevens
authors.affiliation: 1 Centre for Human Drug Research, Leiden, the Netherlands.
authors.forename: Joop Ma
authors.initials: JM
authors.lastname: van Gerven
authors.affiliation: 2 UCB Pharma, Braine-l'Alleud, Belgium.
authors.forename: Armel
authors.initials: A
authors.lastname: Stockis
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D001288:Attention / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005133:Eye Movements / Q000187:drug effects*; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects*; D008875:Middle Aged; D004856:Postural Balance / Q000187:drug effects*; D011597:Psychomotor Performance / Q000502:physiology*; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D002492:Central Nervous System Depressants; D011760:Pyrrolidinones; D000431:Ethanol; C482793:brivaracetam
keywords: Brivaracetam; alcohol; epilepsy; ethanol interaction