Pharmacokinetics and metabolism of 14C-brivaracetam, a novel SV2A ligand, in healthy subjects.

Article Details

Citation

Sargentini-Maier ML, Espie P, Coquette A, Stockis A

Pharmacokinetics and metabolism of 14C-brivaracetam, a novel SV2A ligand, in healthy subjects.

Drug Metab Dispos. 2008 Jan;36(1):36-45. Epub 2007 Oct 1.

PubMed ID
17908923 [ View in PubMed
]
Abstract

This study was designed to investigate the human absorption, disposition, and mass balance of (14)C-brivaracetam, a novel high affinity SV2A ligand with potent anticonvulsant activity. Six healthy male subjects received a single p.o. dose of (14)C-brivaracetam (150 mg, 82 microCi, or 3.03 MBq). Serial blood and complete urine and feces were collected until 144 h postdose. Expired air samples were obtained until 24 h. Brivaracetam was rapidly absorbed, with C(max) of 4 mug/ml occurring within 1.5 h of dosing. Unchanged brivaracetam amounted to 90% of the total plasma radioactivity, suggesting a modest first-pass effect. Plasma protein binding of radioactivity was low (17.5%). Urinary excretion exceeded 90% after 2 days, and the final mass balance reached 96.8% of the radioactivity in urine and 0.7% in feces. Only 8.6% of the radioactive dose was recovered in urine as unchanged brivaracetam, the remainder being identified as non-cytochrome P450 (P450)- and P450-dependent biotransformation products resulting from hydrolysis of the amide moiety (M9, 34.2%), hydroxylation of the n-propyl side chain (M1b, 15.9%), and a combination of these two pathways leading to the hydroxy acid (M4b, 15.2%). Minor amounts of taurine and glucuronic acid conjugates and other oxidized derivatives were also identified. Brivaracetam is completely absorbed, is weakly bound to plasma proteins, extensively biotransformed through several metabolic pathways, and eliminated renally.

DrugBank Data that Cites this Article

Drugs
Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
BrivaracetamCytochrome P450 2B6ProteinHumans
No
Substrate
Details
BrivaracetamCytochrome P450 2C19ProteinHumans
No
Substrate
Details
BrivaracetamCytochrome P450 3A4ProteinHumans
No
Substrate
Details