Pharmacokinetics and Metabolism of ¹⁴C-Brivaracetam, a Novel SV2A Ligand, in Healthy Subjects

Abstract

ABSTRACT:This study was designed to investigate the human absorption, disposition, and mass balance of 14

Progress report on new antiepileptic drugs: A summary of the Twelfth Eilat Conference (EILAT XII)

“…Brivaracetam is rapidly and almost completely absorbed after oral administration, and gastrointestinal absorption is unaffected by food (Rolan et al, 2008;Sargentini-Maier et al, 2007;Sargentini-Maier et al, 2008). Brivaracetam is weakly bound to plasma proteins (~17.5%), and its half-life is about 8 h. Brivaracetam is renally excreted following extensive metabolism, primarily by hydrolysis and to a lesser extent by CYP-dependent hydroxylation Sargentini-Maier et al, 2008).…”

Brivaracetam

“…The volume of distribution is 0.5 L/kg, a value that is close to the volume of distribution of total body water [22].…”

“…Excretion in expired air is undetectable. After administration of radiolabelled drug, the main circulating species is unchanged brivaracetam, amounting to 90% of the total plasma radioactivity [22]. The major metabolic pathways include hydrolysis of the acetamide group, hydroxylation mediated by several cytochrome P450 (CYP) enzymes (CYP2C19, CYP2C9, CYP3A4, with minor contributions of CYP2C8 and CYP2B6) and a combination of these (UCB, data on fi le).…”

“…More than 95% of a radioactive dose is recovered in urine within 72 h, as the acidic (M9: 34.2% of the dose), ω-1 hydroxylated (M1b: 15.9%), and ω-1 hydroxylated acid (M4b: 15.2%) metabolites, and 8.6% as the parent drug ( Fig. 35.2) [22]. There is no evidence of brivaracetam undergoing chiral inversion (i.e.…”

Innovations in Epilepsy Management – An Overview

“…Brivaracetam is currently undergoing an intensive clinical assessment in adults with partial onset seizures and as an add-on treatment in adolescents and adults aged 16-65 years with refractory partial onset seizures. It is reported to cause a mere decrease in serum phenytoin levels and carbamazepine area under the curve (AUC) levels (73 (74).…”