Drug characteristics derived from kinetic modeling: combined ¹¹C-UCB-J human PET imaging with levetiracetam and brivaracetam occupancy of SV2A.

ABSTRACT:

Background

Antiepileptic drugs, levetiracetam (LEV) and brivaracetam (BRV), bind to synaptic vesicle glycoprotein 2A (SV2A). In their anti-seizure activity, speed of brain entry may be an important factor. BRV showed faster entry into the human and non-human primate brain, based on more rapid displacement of SV2A tracer ¹¹C-UCB-J. To extract additional information from previous human studies, we developed a nonlinear model that accounted for drug entry into the brain and binding to SV2A using brain ¹¹C-UCB-J positron emission tomography (PET) data and the time-varying plasma drug concentration, to assess the kinetic parameter K₁ (brain entry rate) of the drugs.

Method

Displacement (LEV or BRV p.i. 60 min post-tracer injection) and post-dose s

SUBMITTER: Naganawa M 

PROVIDER: S-EPMC9643320 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature