2022
Drug characteristics derived from kinetic modeling: combined 11C-UCB-J human PET imaging with levetiracetam and brivaracetam occupancy of SV2A
Naganawa M, Gallezot J, Finnema S, Maguire R, Mercier J, Nabulsi N, Kervyn S, Henry S, Nicolas J, Huang Y, Chen M, Hannestad J, Klitgaard H, Stockis A, Carson R. Drug characteristics derived from kinetic modeling: combined 11C-UCB-J human PET imaging with levetiracetam and brivaracetam occupancy of SV2A. EJNMMI Research 2022, 12: 71. PMID: 36346513, PMCID: PMC9643320, DOI: 10.1186/s13550-022-00944-5.Peer-Reviewed Original ResearchTime-activity curvesBrain entryDrug concentrationsNon-human primate brainAnti-seizure activitySynaptic vesicle glycoprotein 2APlasma drug concentrationsPrevious human studiesBackgroundAntiepileptic drugsHealthy subjectsBlood samplesHuman studiesLevetiracetamPrimate brainEmission tomography dataBrivaracetamDistribution volumeArterial input functionBrainDrug characteristicsPositron emission tomography dataDrug entryFree fractionDrugsKinetic parameters k1
2015
Brivaracetam, a selective high‐affinity synaptic vesicle protein 2A (SV2A) ligand with preclinical evidence of high brain permeability and fast onset of action
Nicolas JM, Hannestad J, Holden D, Kervyn S, Nabulsi N, Tytgat D, Huang Y, Chanteux H, Staelens L, Matagne A, Mathy FX, Mercier J, Stockis A, Carson RE, Klitgaard H. Brivaracetam, a selective high‐affinity synaptic vesicle protein 2A (SV2A) ligand with preclinical evidence of high brain permeability and fast onset of action. Epilepsia 2015, 57: 201-209. PMID: 26663401, DOI: 10.1111/epi.13267.Peer-Reviewed Original ResearchConceptsFaster onsetAcute seizuresHigh-affinity synaptic vesicle protein 2A ligandNonhuman primate PET studyAudiogenic seizure miceRapid brain entryOnset of actionSingle oral dosingHigh brain permeabilityBlood-brain barrier permeability (BBBP) valuesPrimate PET studyAudiogenic miceBrain entryCaco-2 cellsSeizure micePreclinical evidenceAntiepileptic drugsSusceptible miceBrain levelsBrain penetrationPreclinical dataBrain kineticsOral dosingSingle dosingClinical studies